Kaiser Permanente San Diego Medical Center

BACKGROUND: In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. METHODS: We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon. CONCLUSIONS: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon. (Funded by Gilead Sciences; FISSION and NEUTRINO ClinicalTrials.gov numbers, NCT01497366 and NCT01641640, respectively.).

OBJECTIVE: The purpose of this study was to describe the development of the Diabetes Distress Scale (DDS), a new instrument for the assessment of diabetes-related emotional distress, based on four independent patient samples. RESEARCH DESIGN AND METHODS: In consultation with patients and professionals from multiple disciplines, a preliminary scale of 28 items was developed, based a priori on four distress-related domains: emotional burden subscale, physician-related distress subscale, regimen-related distress subscale, and diabetes-related interpersonal distress. The new instrument was included in a larger battery of questionnaires used in diabetes studies at four diverse sites: waiting room at a primary care clinic (n = 200), waiting room at a diabetes specialty clinic (n = 179), a diabetes management study program (n = 167), and an ongoing diabetes management program (n = 158). RESULTS: Exploratory factor analyses revealed four factors consistent across sites (involving 17 of the 28 items) that matched the critical content domains identified earlier. The correlation between the 28-item and 17-item scales was very high (r = 0.99). The mean correlation between the 17-item total score (DDS) and the four subscales was high (r = 0.82), but the pattern of interscale correlations suggested that the subscales, although not totally independent, tapped into relatively different areas of diabetes-related distress. Internal reliability of the DDS and the four subscales was adequate (alpha > 0.87), and validity coefficients yielded significant linkages with the Center for Epidemiological Studies Depression Scale, meal planning, exercise, and total cholesterol. Insulin users evidenced the highest mean DDS total scores, whereas diet-controlled subjects displayed the lowest scores (P < 0.001). CONCLUSIONS: The DDS has a consistent, generalizable factor structure and good internal reliability and validity across four different clinical sites. The new instrument may serve as a valuable measure of diabetes-related emotional distress for use in research and clinical practice.

We followed 292 patients who had sustained an acute traumatic hemarthrosis for a mean of 64 months. The KT-1000 arthrometer measurements within 90 days of injury revealed the injured knee was stable in 56 patients and unstable in 236. Forty-five unstable patients had an ACL reconstruction within 90 days of injury. Surgical procedures performed > 90 days after injury included ligament reconstruction in 46 patients. Factors that correlated with patients who had late surgery for a meniscal tear or an ACL reconstruction (P < 0.05) were preinjury hours of sports participation, arthrometer measurements, and patient age. Follow-up data are presented for the patients divided into four groups: I, early stable, no reconstruction; II, early unstable, no reconstruction; III, early reconstruction; and IV, late reconstruction. No patient changed occupation because of the knee injury. Hours per year of sports participation and levels of sports participation decreased in all groups. Joint arthrosis was documented by radiograph and bone scan. Joint surface injury abnormalities observed at surgery and meniscal surgery showed greater abnormalities by radiograph and bone scan scores (P < 0.05). Reconstructed patients had a higher level of arthrosis by radiograph and bone scan.

BACKGROUND: Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. METHODS: At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 microg per kilogram of body weight per week or a low dose of 1.0 microg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 microg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen. RESULTS: Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P=0.20 for standard-dose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], -2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and -1.1% (95% CI, -5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. CONCLUSIONS: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials.gov number, NCT00081770.)

BACKGROUND: It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma. METHODS: We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 mug twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year. RESULTS: During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P=0.006) and a lower rate of exacerbations (P<0.001) and of supplementary use of controller medication (P<0.001). In the inhaled-corticosteroid group, as compared with the placebo group, the mean increase in height was 1.1 cm less at 24 months (P<0.001), but by the end of the trial, the height increase was 0.7 cm less (P=0.008). During treatment, the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth, albeit temporarily and not progressively. CONCLUSIONS: In preschool children at high risk for asthma, two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued. (ClinicalTrials.gov number, NCT00272441.).

OBJECTIVE: To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. METHODS: Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). RESULTS: Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with >or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). CONCLUSIONS: Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

OBJECTIVES: Population-based data on the epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage (ALGIH) are lacking. This survey of the incidence, etiology, therapy, and long-term outcome of patients with ALGIH was conducted in a defined population. METHODS: In a large health maintenance organization, discharge data and colonoscopy records were used to identify adults hospitalized with ALGIH from 1990 to 1993. Data were collected by record review and telephone calls. RESULTS: Two hundred nineteen patients had 235 hospitalizations, yielding an estimated annual incidence rate of 20.5 patients/100,000 (24.2 in males versus 17.2 in females, p < .001). The rate increased > 200-fold from the third to the ninth decades of life. Diagnoses were: colonic diverticulosis, 91 (41.6%); colorectal malignancy, 20 (9.1%); ischemic colitis, 19 (8.7%); miscellaneous, 63 (28.8%); and unknown, 26 (11.9%). Eight (3.6%) patients died in the hospital (5 of 206 (2.4%) with hemorrhage before admission versus 3 of 13 (23.1%) with hemorrhage after admission, p < .001). Follow-up of 210 of 211 (99.5%) survivors was 34.0 +/- 1.1 months. In the 83 diverticulosis patients without definitive therapy, the hemorrhage recurrence rate (Kaplan-Meier method) was 9% at 1 year, 10% at 2 years, 19% at 3 years, and 25% at 4 years. In the 89 diverticulosis patients who survived hospitalization, all-cause mortality rates (none from hemorrhage) were 11% at 1 year, 15% at 2 years, 18% at 3 years, and 20% at 4 years. CONCLUSIONS: Hospitalization with ALGIH is related to age and male gender. After hemorrhage from colonic diverticulosis, the leading cause, rates of ALGIH recurrence and unrelated death are similar during the next 4 years.

UNLABELLED: Between 1982 and 1986, 126 patients who had undergone ACL reconstruction were followed in a prospective manner. One year follow-up statistics were reviewed for the presence of 13 different complications. The most prevalent complications were quadriceps weakness, flexion contracture, and patellofemoral pain. Quadriceps weakness (strength less than 80% of the normal side) was present in 65% of patients and correlated positively with flexion contracture, patellar irritabibilty, and ACL reconstructions using patellar tendon grafts. Flexion contracture of 5 degrees or more was present in 24% of patients and correlated positively with increased age and patellar irritability. Patellofemoral pain was present in 19% of patients and correlated positively with flexion contracture. CLINICAL RELEVANCE: The three most common complications of knee ligament surgery are shown to be strongly interrelated. It is likely that a causal relationship is present in which flexion contracture causes patellofemoral irritability, and that both of these factors, alone or in combination, result in quadriceps weakness. If this theory is correct, then it is crucial that postoperative rehabilitation programs place a major emphasis on the avoidance of flexion contracture.

BACKGROUND: The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. RESULTS: The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. (Funded by AbbVie; PEARL-III and PEARL-IV ClinicalTrials.gov numbers, NCT01767116 and NCT01833533.).

OBJECTIVES: To obtain epidemiological data on hospitalization for acute upper gastrointestinal hemorrhage (AUGIH) in a demographically defined population. METHODS: Adults hospitalized in 1991 with AUGIH [from a San Diego health maintenance organization (270,699 adult members)] were identified from discharge codes in the International Classification of Diseases, 9th Revision, Clinical Modifications, and their records were reviewed. RESULTS: There were 276 hospitalizations among 258 patients, an annual incidence rate of 102.0 hospitalizations per 100,000. Patient analysis, including the first admission of 15 patients with multiple hospitalizations, revealed rates of 128.3 in males and 65.8 in females. The rate increased with age in males (p = 0.008) and females (p = 0.001) more than 30-fold between the 3rd and 9th decades of life. AUGIH started before admission in 242 (93.8%) patients and after admission for other disorders in 16 (6.2%) patients. Endoscopy was performed in 241 (93.4%) patients. Diagnoses were: peptic ulcer, 159 (61.6%); mucosal erosive disease, 37 (14.3%); varices, 16 (6.2%); miscellaneous, 25 (9.7%); and unknown, 21 (8.1%). Peptic ulcer patients were similar to other patients (mean +/- SE) in age [60.6 +/- 1.2 vs. 60.7 +/- 1.5 yr] and gender [104 (65.4%) vs. 60 (60.6%) males], but were more often nonsteroidal anti-inflammatory drug (NSAID)-users [87 (54.7%) vs. 34 (34.3%) (p = 0.002)]. Older age, female gender, and NSAID use independently predicted gastric ulcer (p < or = 0.03). The severity of bleeding was similar in patients with peptic ulcers and in those with mucosal erosive disease and was not related to NSAID use in peptic ulcer patients. Patients whose AUGIH started after admission were older than those whose AUGIH began before admission [70.4 +/- 2.9 vs. 60.0 +/- 1.0 yr (p = 0.002)], and they had a higher mortality rate [4 (25%) vs. 9 (3.7%) (p = 0.005)]. CONCLUSIONS: 1) The annual incidence of hospitalization for AUGIH was 102.0 per 100,000, increased markedly with age, and was twice as high in males as in females. 2) Peptic ulcer was the most common cause. 3) Gastric ulcer was associated with older age, female gender, and NSAID use. 4) Mortality rates were high when AUGIH started after hospitalization for another disorder.

BACKGROUND: Deep surgical site infection following total knee arthroplasty is a devastating complication. Patient and surgical risk factors for this complication have not been thoroughly examined. The purpose of this study was to evaluate risk factors associated with deep surgical site infection following total knee arthroplasty in a large U.S. integrated health-care system. METHODS: A retrospective review of a prospectively followed cohort of primary total knee arthroplasties recorded in a total joint replacement registry from 2001 to 2009 was conducted. Records were screened for deep surgical site infection with use of a validated algorithm, and the results were adjudicated by chart review. Patient factors, surgical factors, and surgeon and hospital characteristics were identified with use of the total joint replacement registry. Cox regression models were used to assess risk factors associated with deep surgical site infection. RESULTS: A total of 56,216 total knee arthroplasties were identified; 63.0% were done in women, the average age of the patients was 67.4 years (standard deviation [SD] = 9.6), and the average body mass index (BMI) was 32 kg/m2 (SD = 6). The incidence of deep surgical site infection was 0.72% (404/56,216). In a fully adjusted model, patient factors associated with deep surgical site infection included a BMI of ≥35 (hazard ratio [HR] = 1.47), diabetes mellitus (HR = 1.28), male sex (HR = 1.89), an American Society of Anesthesiologists (ASA) score of ≥3 (HR = 1.65), a diagnosis of osteonecrosis (HR = 3.65), and a diagnosis of posttraumatic arthritis (HR = 3.23). Hispanic race was protective (HR = 0.69). Protective surgical factors included use of antibiotic irrigation (HR = 0.67), a bilateral procedure (HR = 0.51), and a lower annual hospital volume (HR = 0.33). Surgical risk factors included quadriceps-release exposure (HR = 4.76) and the use of antibiotic-laden cement (HR = 1.53). In a subanalysis, operative time was a risk factor, with a 9% increased risk per fifteen-minute increment. CONCLUSIONS: Use of a comprehensive infection surveillance system, combined with a total joint replacement registry, identified patient and surgical factors associated with infection following total knee arthroplasty in a large sample. High-risk patients should be counseled, and modifiable clinical conditions should be optimized. Use of antibiotic irrigation should be encouraged, but antibiotic-laden cement may not be useful. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

The provision of patient-centered care requires a health care environment that fosters engagement between patients and their health care team. One way to encourage patient-centered care is to incorporate patient-reported outcomes into clinical settings. Collecting these outcomes in routine care ensures that important information only the patient can provide is captured. This provides insights into patients' experiences of symptoms, quality of life, and functioning; values and preferences; and goals for health care. Previously embraced in the research realm, patient-reported outcomes have started to play a role in successful shared decision making, which can enhance the safe and effective delivery of health care. We examine the opportunities for using patient-reported outcomes to enhance care delivery and outcomes as health care information needs and technology platforms change. We highlight emerging practices in which patient-reported outcomes provide value to patients and clinicians and improve care delivery. Finally, we examine present and future challenges to maximizing the use of patient-reported outcomes in the clinic.

BACKGROUND: Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial. METHODS: A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy. RESULTS: Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms. CONCLUSIONS: Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.

BACKGROUND: The proportion of overweight adolescents has increased, but the behavioral risk factors for overweight youth are not well understood. OBJECTIVE: To examine how diet, physical activity, and sedentary behaviors relate to overweight status in adolescents. DESIGN AND SETTING: Baseline data from the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition Project, a randomized controlled trial of adolescents to determine the effects of a clinic-based intervention on physical activity and dietary behaviors. PARTICIPANTS: A total of 878 adolescents aged 11 to 15 years, 42% of whom were from minority backgrounds. MAIN OUTCOME MEASURE: Centers for Disease Control and Prevention body mass index-for-age percentiles divided into 2 categories: normal weight (<85th percentile) and at risk for overweight plus overweight (AR + O) (>or=85th percentile). RESULTS: Overall, 45.7% of the sample was classified as AR + O with a body mass index for age at the 85th percentile or higher. More girls from minority backgrounds (54.8%) were AR + O compared with non-Hispanic white girls (42%) (chi(2)(1) = 7.6; P =.006). Bivariate analyses indicated that girls and boys in the AR + O group did fewer minutes per day of vigorous physical activity, consumed fewer total kilojoules per day, and had fewer total grams of fiber per day than those in the normal-weight group. Boys in the AR + O group also did fewer minutes per day of moderate physical activity and watched more minutes per day of television on nonschool days than normal-weight boys. Final multivariate models indicated that independent of socioeconomic status (as assessed by household education level), girls had a greater risk of being AR + O if they were Hispanic or from another minority background (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.09-2.49) and a reduced risk of being AR + O as minutes per day of vigorous physical activity increased (OR = 0.93; 95% CI, 0.89-0.97). A low level of vigorous physical activity was the only significant risk factor for boys being AR + O (OR = 0.92; 95% CI, 0.89-0.95). Analyses based on meeting behavioral guidelines supported these findings and showed that failing to meet the 60 min/d moderate to vigorous physical activity guideline was associated with overweight status for both girls and boys. In addition, boys who failed to meet sedentary behavior and dietary fiber guidelines were more likely to be overweight. CONCLUSIONS: Of the 7 dietary and physical activity variables examined in this cross-sectional study, insufficient vigorous physical activity was the only risk factor for higher body mass index for adolescent boys and girls. Prospective studies are needed to clarify the relative importance of dietary and physical activity behaviors on overweight in adolescence.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

BACKGROUND: Adherence to dementia guidelines is poor despite evidence that some guideline recommendations can improve symptoms and delay institutionalization of patients. OBJECTIVE: To test the effectiveness of a dementia guideline-based disease management program on quality of care and outcomes for patients with dementia. DESIGN: Clinic-level, cluster randomized, controlled trial. SETTING: 3 health care organizations collaborating with 3 community agencies in southern California. PARTICIPANTS: 18 primary care clinics and 408 patients with dementia age 65 years or older paired with 408 informal caregivers. INTERVENTION: Disease management program led by care managers and provided to 238 patient-caregiver pairs at 9 intervention clinics for more than 12 months. MEASUREMENTS: Adherence to 23 guideline recommendations (primary outcome) and receipt of community resources and patient and caregiver health and quality-of-care measures (secondary outcomes). RESULTS: The mean percentage of per-patient guideline recommendations to which care was adherent was significantly higher in the intervention group than in the usual care group (63.9% vs. 32.9%, respectively; adjusted difference, 30.1% [95% CI, 25.2% to 34.9%]; P < 0.001). Participants who received the intervention had higher care quality on 21 of 23 guidelines (P < or = 0.013 for all), and higher proportions received community agency assistance (P < or = 0.03) than those who received usual care. Patient health-related quality of life, overall quality of patient care, caregiving quality, social support, and level of unmet caregiving assistance needs were better for participants in the intervention group than for those in the usual care group (P < 0.05 for all). Caregiver health-related quality of life did not differ between the 2 groups. LIMITATIONS: Participants were well-educated, were predominantly white, had a usual source of care, and were not institutionalized. Generalizability to other patients and geographic regions is unknown. Also, costs of a care management program under fee-for-service reimbursement may impede adoption. CONCLUSIONS: A dementia guideline-based disease management program led to substantial improvements in quality of care for patients with dementia. Current Controlled Trials identifier: ISRCTN72577751.

INTRODUCTION This clinical guideline was designed to address colon ischemia (CI) including its definition, epidemiology, risk factors, presentations, methods of diagnosis, and therapeutic interventions. Each section of the document will present key recommendations or summary statements followed by a comprehensive summary of supporting evidence. An overall summary of all recommendations is listed in Table 1.Table 1: Recommendations and summary statementsTable 1: Continued.A search of MEDLINE (1946 to present) and EMBASE (1980 to present) with language restriction to English was conducted using the search terms ischemic colitis, ischaemic colitis, colon ischemia, colonic ischemia, colon ischaemia, colonic ischaemia, colon gangrene, colonic gangrene, colon infarction, colonic infarction, rectal ischemia, rectal ischaemia, ischemic proctitis, ischaemic proctitis, cecal ischemia, cecal ischaemia, ischemic colon stricture, ischaemic colon stricture, ischemic colonic stricture, ischaemic colonic stricture, ischemic megacolon, ischaemic megacolon, colon cast, and colonic cast. The references obtained were reviewed and the best studies were included as evidence for guideline statements or in the absence of quality evidence, expert opinion was offered. The GRADE system (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the quality of evidence and strength of recommendations (1, 2). The level of evidence ranged from “high” (implying that further research was unlikely to change the authors’ confidence in the estimate of the effect) to “moderate” (further research would be likely to have an impact on the authors’ confidence in the estimate of effect) to “low” (further research would be expected to have an important impact on the authors’ confidence in the estimate of the effect and would be likely to change the estimate) to “very low” (any estimate of effect is very uncertain). The strength of a recommendation was graded as “strong” when the desirable effects of an intervention clearly outweighed the undesirable effects and as “conditional” when there was uncertainty about the tradeoffs between the desirable and undesirable effects of an intervention. Of note, in this clinical guideline there are several sections focusing on factors associated with prognosis in CI. Because the GRADE system currently is not designed to rate the quality of the literature for these topics, we have preceded each of these sections with “summary statements” that detail the most important concepts regarding each area, but without a GRADE rating. DEFINITION CI is the condition that results when blood flow to the colon is reduced to a level insufficient to maintain cellular metabolic function. The end result of this process is that colonocytes become acidotic, dysfunctional, lose their integrity and, ultimately, die. Although the etymologic root of the word ischemia is from the Greek iskhaimos, meaning a “stopping of the blood,” we now know that blood flow need not stop but only diminish significantly to cause ischemic damage. Moreover, ischemia may be followed by reperfusion injury and, for relatively brief periods of ischemia, this combined injury may produce more damage than just reduction of blood flow without reperfusion. The degree to which colonic blood flow must diminish before ischemia results varies with the acuteness of the event, the degree of preexisting vascular collateralization, and the length of time the low flow state persists. CI may manifest with reversible or irreversible damage. Reversible damage includes colopathy, i.e., subepithelial hemorrhage or edema, and colitis; colitis reflects an evolutionary stage in which the overlying mucosa ulcerates as the subepithelial edema and blood are resorbed. In reversible disease, such resorption occurs rather promptly, usually within 3 days. Ulcerations may persist for several months before resolving, although during this time, the patient usually is asymptomatic. Irreversible manifestations of CI include gangrene, fulminant colitis, stricture formation, and, rarely, chronic ischemic colitis. Recurrent sepsis due to bacterial translocation is another rare manifestation of irreversibly damaged bowel. EPIDEMIOLOGY The absence of a unique diagnosis code for acute large bowel ischemia in the ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) challenges case finding for research. This system, which is commonly used in the United States, assigns the hospital discharge code 557.0 (acute vascular insufficiency of intestine) and 557.9 (unspecified vascular insufficiency of intestine) to ischemic colitis as well as many other small and large bowel entities. This limitation persists in the newer ICD-10-CM classification system. Therefore, either medical records must be reviewed carefully or clear stipulations must be applied to databases to reliably identify with CI the we to ischemic colitis not have a of disease, is the in of all for acute CI or in large of with CI an rate of In the of in the the was Because of of the rate was with of for or medical of another an of with a with CI are only but CI occurs in of all and with An an of only although of of were this relatively low CI is more in than in and of in large have that was and that most and all were to be in large from to but case and of and in these studies Recurrent CI for and were and in and and in another have with disease, such as Therefore, in large will be to the of with and with likely to CI result from in the or from or in the the cause is to be and reperfusion In most cause for ischemia is and such are to ischemia, likely a result of are as in the is and most commonly an of or This classification for CI is used in clinical but in with have the CI is in a and An of of CI is on with clinical manifestations of and in the are not including of small and of the of the rectal associated with CI. The colon is to ischemia, to its relatively low blood its unique in blood flow during periods of and its to the of usually is not statements and of CI in with clinical of bowel and be in to have CI is in with a of is and chronic are associated with from CI for be in with CI and in all with CI in which the such as and other of CI in with clinical In of a of and be and of evidence large studies of risk factors for CI associated medical and and of The used in these studies risk factors rather than only to that a risk of the of other of these studies must be in of the in factors and other in research Table the for which the most in of research methods and of are of relatively on medical without comprehensive on of rather than or records and of from ICD-9-CM by such as and Because studies not and during a before the of the have by risk to that or acute of including rectal colitis and of and are on the of important that have low of or or are from Moreover, all studies are in as well as not and patient may be result in of CI in with a such as likely more than is important to that not and associated with colon ischemia in of and risk factors for CI are by the in chronic vascular and CI and were as in with ischemia with other of CI that are and in with a a of in of with or Although all of these many of the that be by and CI within 3 of acute in of and and were in with than in with either CI or with with CI more or than with other colonic of hemorrhage and chronic in from in and the in and CI with acute to the effects of and and to the risk of CI associated with including although of with these is another risk in as a risk for CI used to with was from the of of CI during the months its in In a medical of of the of CI was in with than without In another the risk for CI was and for with and than for these studies applied more to the of as a risk for studies risk including that an in only and the risk in in the the most vascular in the that the of CI in only of but a during the before in of risk and reduced blood flow as a result of and the of CI be a clinical for was a risk in as with CI have a diagnosis applied to with as a risk for CI from but not as an in In absence of in its in chronic was present in of from and was 3 as in with as other in that to the of and of of CI by were of the by and in 3 as many on than in other The most although in on in CI is in with a in blood with the was as in with CI as was in with other colonic and CI in with acute is another risk for CI. are case of in with including of and In the of the vascular in small but more ischemia than CI were in of blood of from and in of blood the diagnosis of CI associated with and vascular were in more with CI than in about an to these include uncertainty regarding the to CI or were of is to a for in of the of many CI and the low rate of CI. In of with CI reduced of that as a result of its to an of reduced of and reduced or a about the or this time, for a in most with CI not although in with CI and in with a of CI have in were of most of were CI the colon in and to the in 3 of in CI was to the of the ischemic and a and of with of is a cause of and in with cause CI. Of the were of and the from to 3 colon and of CI in with a with of CI of and a CI is only as an for but the rate of this CI be in with a of are of CI followed such include patient other CI result from reduced colonic blood flow as a of and of which are more with by than by have other with CI including colon and, a to the and of for an overall rate of CI of with of with and with that CI occurs more than CI of preceded CI in only of all of CI in for CI these vascular is of the as a risk a confidence but not the confidence of the CI in have for colon CI was reviewed in there was evidence to of as to CI have more evidence for the of and other including that and are best as but there is for a of many to to estimate of evidence and on the clinical factors associated with there are risk factors for CI in most and have risk The risk factors for CI its and the of of the and in patient with CI. research the cause of CI and its risk factors is Recommendations The diagnosis of CI is usually of including an to and within of or blood or very low level of diagnosis of be when present with very low level of CI to the colon is associated with with other of CI of evidence CI with an to and within of or blood or and a large of with CI in which the most of were rectal and of with CI that and were the most need to and are the and all in this in of and and is usually to although of its not to is usually present the of with more commonly have than rectal only of with have rectal and the diagnosis of for with have the clinical associated with such as and or The of is to in with CI the and of from the time to for a of with within of and within 3 of In more than of the of the is of CI within and the colon in may to months for the colon to during this time the patient is usually asymptomatic. is usually in but in of with were to have CI as the cause was more in and in with disease, and and on The for and of hospital were for with CI with other of hemorrhage occurs in with fulminant and that of their overall of with CI a level of to the rate of low in a more is in of present with CI of CI are and and only a of are The of that colitis and fulminant colitis are in and of that persist for more than are associated with a of acute and irreversible disease, such as and colitis, or of with not the of to and than of from of the of have the of the of of each of these clinical and that is used as a with expert opinion for the clinical of an colonic or not by of is a rare of CI that in the literature in This usually occurs in with medical or such of CI the of the colon and have that the the of of to in length is the acute ischemic may of mucosa with or without or may be in which case a of is the intervention. CI with the and of the The injury is and hemorrhage and edema, with or without and of the may be and with more and may In of the is by a stricture, most of which are is more in with and was in of was not in patient with disease, these were on or The studies clear of stricture, and these stricture are likely are but further is to this with that of stricture CI bowel with chronic and The most of ischemic damage colitis is by and is in the of these but rectal is acute without rectal and are the most clinical of of a colitis with of and a are of fulminant colitis, a rare of CI. The is with this CI of and rectal with on are the most of fulminant colitis CI of evidence The colon is most commonly but colonic is from In a large of all of their colon by or or in in all of CI was by a was the colon was most followed by the colon colon and colon In this although was associated with and were in with and was associated more in with and chronic on results were in large studies in and This of to be as a of a of although in this there were between and CI in clinical presentations, risk factors, or the of with were more likely to have of colon ischemia of CI be by the vascular of the colon and blood flow is by the and the is and unique of the colon are that are to ischemic as a result of their between vascular include the and colon the there may be of to the of the which is a of the with the of the which is from the to the from the an that to the to ischemic The is by ischemia of its relatively blood from and In were to ischemic the and of the the that the length of colon reflects the cause of with and of commonly of further to their The of CI for but only that a clinical and than CI other of the colon with present most commonly with acute without rectal although when may be with have disease, and chronic more than with CI other of the colon with CI and that with all other colon for need for intervention and were in a more of with in which the rate was for with in with The of in several other an for of with for CI that the of the colon another an of for with in cecal was in case of with acute of with either in bowel or the of each patient was with the including cecal or of the a of or although evidence of or the time of and there was for the ischemic is to this rare of CI is a of with a The of CI a prognosis to that of a rate of in colon was by CI. In this stage chronic and vascular were the most and sepsis was the most and that of of CI that intervention either or of The of these was associated with a of for CI that or to is there was in the and and the risk factors associated with such an likely a CI of evidence of CI is to when a patient that and the patient with and another diagnosis of CI. the and of is the usually of CI and the that many with may not medical there is a of in the that address have in the time studies and within studies with a have detail of CI that from to a of were to a with CI and that of a of their CI with a of Of of a and patient a of a rate of with a of months but only evidence of This just as with the the most of are and although the of these was not of during a in in CI with CI an and were more in the other in clinical or of the time of diagnosis were rate was in a of with a of months with and were and more likely to have a The of and of more than a rate of the that and were more in the than in the with only a In although of CI to be and the and to be the as of the time to to be The of CI a chronic colitis of of this colitis be by more than 3 months of and evidence with or of CI. The in the literature and not a such as the and, of this is The of and to followed by is the most although rectal without is Recurrent and of an of colitis that is a of for colonic of the of chronic ischemic colitis are and from an to a rate of and are likely that of their chronic but this for diagnosis, the of in studies detail of to but these were in an were on and likely diagnosis without would not the of by and that small and may an in vascular for is further by studies that occurs in with of or and that a effect on the of that or more of CI the of chronic colitis an by of with chronic CI that of from a This finding in this rare of the of an for chronic CI. In a in of of colitis and that of CI by a of and and that of these with of disease, or colitis. of this was its and the to an cause for the chronic colitis in each In the chronic CI but their was by including within of and to on the of of chronic colitis with the time of and evidence of chronic colitis in their of that a chronic colitis be the process between an diagnosis of CI and the of a stricture, but the studies that this to the time when the chronic colitis be a studies the as during the time and not of colitis before stricture this time, there are insufficient to chronic CI as a unique and further is using a more such as the CI statements be to CI low and the of metabolic be used to of CI of evidence this time, there is a of to the and of in but such is a to CI of with CI and the with an that the blood and were in the CI with the The intervention or in with with medical and that only and were in with there were in or with or CI and that and were more in with than in with with that with of and to a with CI and that level was associated with CI with with disease, these studies to identify blood that were associated with the studies were by patient and including and for in and or in or were most in with CI. is to which are most associated with disease, which best and are most and The diagnosis for with and is including disease, colitis, colitis, and colonic for the diagnosis of CI clinical is to be of all to an in that of with and and were with only were the time of the diagnosis and the of diagnosis clinical for CI with and studies is very the diagnosis, blood comprehensive metabolic for and and and blood is to the for and the level to blood although not usually significantly from in with CI. from the patient is acidotic, although and will the and and for of are important In small was by from colon in with CI this may be for CI and be for in all with Although with its and be of the for with in have to be associated with acute bowel ischemia of these evidence that during the may the the and of and studies for colon ischemia CI Recommendations with and be as the of for with to the and of colitis level of The diagnosis of CI be on bowel edema, and be on patient with or in patient in the of be level of or of colonic and be used to the of colonic level of In a patient in the of CI may be a of acute ischemia without and and the is for vascular disease, be for further low level of of evidence of methods have used to including of the and or the diagnosis, but have that are to a diagnosis, when of the that the of a colon and with of the colon are of ischemic and In of were present in of with CI and patient the of more reversible CI was in by with the the for The of CI was of that were by subepithelial and that either in or to a colitis with several a in diagnosis and by and of the and to of the mucosa for is now used to the of ischemic although or other be used for this as In the the patient the of there are to a for to the mucosa to is commonly obtained in the to not obtained the this when are as either or CI as in Table and of are the risk for and further of the is to is to medical other than CI the diagnosis of and which of the colon are and with or without are associated with but are not to a with or without or of disease, to the or were and with colitis and within of of ischemia as the and of colitis was in in the of bowel was in with colitis, and as well as in CI. This that the of colitis are and not unique for CI in most with Classification of and and of colon ischemia (CI) blood blood of bowel in CI usually results from subepithelial edema hemorrhage and reflects the degree of ischemia and the time between the ischemic and of a case of with CI. The the the of the in to the was in of and as a of colonic with of this to the acute reperfusion of ischemic bowel. was in of and as and with of the colon and this to the of ischemic damage without reperfusion. The with and colonic Of the overall and a or of the of the bowel that to ischemia and reperfusion of the This to the most in of colon by but for were relatively and there was are in the of that of in with ischemia, ischemia, and In this CI in was the of disease, and the the to of the mucosa and edema of the as a of i.e., the CI in with and acute within of between and and chronic CI between and evidence of vascular the acute was by and bowel bowel in the was not in with vascular in the acute or and in the chronic of these studies for diagnosis of CI using although the ischemic is to the most of CI from each of the ischemic process and of disease, to that reliably CI from other and to of be of CI. of the colon is associated with CI and usually the of ischemic injury is to the be from ischemic of colon by and colonic of of the colon with CI to the the of CI significantly colon and were than with In although was the CI to more the more This is by its small of of of other CI and absence of a but the on between and CI. the although between CI and well as other such as and the colon be for with a several from the ischemic the patient not not be the time of with CI a of colon and is to further damage from the reduction in blood flow that occurs with colon The of CI is usually not but in with risk factors, for the with and acute of evidence of ischemic bowel of ischemia the the most included of bowel a and bowel this was not its to a and of the of on with the most to CI in with risk factors for disease, including CI is usually in but be used to identify or not vascular are the is in to of of and the of such a finding is of the and without this usually with the to the with the of vascular not on the and of for vascular in but a including and studies that in the diagnosis of and vascular the and for diagnosis to be and studies were in in and, their not the of studies in small or a and for vascular in with CI. In to in which or an vascular studies are not in most with CI by the time of colon blood flow usually to and the are not from ischemia but rather the ischemic with or without reperfusion In with disease, such as with or when the between and CI in with and or a is In with be either or before as the colonic may be the of and including a without but with and to the and become for the diagnosis of that in with and with another diagnosis that the for of or although the was for and the was to be and the was This that the of during to the vascular Although this small of a and each of In patient in the of CI may be a of and the is for vascular disease, be for further a not vascular as the is important to that there are as a of that a of with may present within or a the of with of in of most of their small bowel or but of with have and in the in with not or a as Although there are to we that the of a ischemic to the small the of a and are in of CI. In of with ischemia, that and the of and not bowel. In small of with either small or large bowel ischemia, and were associated with bowel in and of with an with a large bowel and cecal of the in of of in with colon and with colon The of for infarction, but very low the of the

BACKGROUND: Asthma is a common condition during pregnancy and may be associated with adverse perinatal outcomes. OBJECTIVE: This meta-analysis sought to establish if maternal asthma is associated with an increased risk of adverse perinatal outcomes, and to determine the size of these effects. SEARCH STRATEGY: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Cohort studies published between 1975 and March 2009 were considered for inclusion. Studies were included if they reported at least one perinatal outcome in pregnant women with and without asthma. DATA COLLECTION AND ANALYSIS: A total of 103 articles were identified, and of these 40 publications involving 1,637,180 subjects were included. Meta-analysis was conducted with subgroup analyses by study design and active asthma management. MAIN RESULTS: Maternal asthma was associated with an increased risk of low birthweight (RR 1.46, 95% CI 1.22-1.75), small for gestational age (RR 1.22, 95% CI 1.14-1.31), preterm delivery (RR 1.41, 95% CI 1.22-1.61) and pre-eclampsia (RR 1.54, 95% CI 1.32-1.81). The relative risk of preterm delivery and preterm labour were reduced to non-significant levels by active asthma management (RR 1.07, 95% CI 0.91-1.26 for preterm delivery; RR 0.96, 95% CI 0.73-1.26 for preterm labour). AUTHOR'S CONCLUSIONS: Pregnant women with asthma are at increased risk of perinatal complications, including pre-eclampsia and outcomes that affect the baby's size and timing of birth. Active asthma management with a view to reducing the exacerbation rate may be clinically useful in reducing the risk of perinatal complications, particularly preterm delivery.

This study describes nurse perceptions about medication errors. Findings reveal that there are differences in the perceptions of nurses about the causes and reporting of medication errors. Causes include illegible physician handwriting and distracted, tired, and exhausted nurses. Only 45.6% of the 983 nurses believed that all drug errors are reported, and reasons for not reporting include fear of manager and peer reactions. The study findings can be used in programs designed to promote medication error recognition and reduce or eliminate barriers to reporting.

A cadaveric model that incorporated quadriceps and hamstrings muscle loads was developed to simulate the squat exercise. The addition of hamstrings load affected knee kinematics in two ways. First, anterior tibial translation during flexion ("femoral roll-back") was significantly reduced (P = 0.003) and second, internal tibial rotation during flexion was reduced (P = 0.008). However, quadriceps force was unaffected by the addition of hamstrings load. Thus, it seems likely that hamstrings muscle activity that has been observed in vivo during a squat probably functions synergistically with the anterior cruciate ligament to provide anterior knee stability. After the ACL was sectioned, anterior tibial translation was significantly increased during the squat (P = 0.04). The anterior cruciate ligament was then reconstructed using a graft instrumented with a load cell. During passive motion, maximal graft tension was at full extension. During simulated squat exercise, the addition of hamstrings caused a significant decrease in graft load (P = 0.006). During the squat, maximal graft tension was at full extension, and was equal to the graft tension at full passive extension. Thus, the squat exercise may be useful in the early stages of anterior cruciate ligament rehabilitation.