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.).

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.

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. 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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.

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.

Keywords: asthma exacerbation; emergency department; Expert Panel Report 3; acute asthma; respiratory failure

PURPOSE: We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence. MATERIALS AND METHODS: This institutional review board approved, multicenter registered trial randomized women with refractory urge incontinence, detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio. Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence. The primary outcome measure was time to failure, as evidenced by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection, or changes in treatment (initiation or increase) at any time after injection. Safety data, including increased post-void residual volume, defined as more than 200 ml irrespective of symptoms, was obtained at specified time points. RESULTS: Approximately 60% of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement. The median duration of their responses was 373 days, significantly longer than the 62 days or less for placebo (p <0.0001). In the botulinum toxin A group increased post-void residual urine (12 of 28 women or 43%) and urinary tract infection in those with increased post-void residual urine (9 of 12 or 75%) exceeded expected ranges. Further injections were stopped after 43 patients were randomized, including 28 to botulinum toxin A and 15 to placebo. CONCLUSIONS: Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder. However, a transient post-void residual urine increase was experienced in 43% of patients. Botulinum toxin A for idiopathic overactive bladder is still under investigation.

Because of scientific fraud four trials have been excluded from the original Cochrane meta-analysis on formulas containing hydrolyzed protein for prevention of allergy and food intolerance in infants. Unlike the conclusions of the revised Cochrane review the export group set up by the Section on Paediatrics, European Academy of Allergology and Clinical Immunology (SP-EAACI) do not find that the exclusion of the four trials demands a change of the previous recommendations regarding primary dietary prevention of allergic diseases. Ideally, recommendations on primary dietary prevention should be based only on the results of randomized and quasi-randomized trials (selection criteria in the Cochrane review). However, regarding breastfeeding randomization is unethical, Therefore, in the development of recommendations on dietary primary prevention, high-quality systematic reviews of high-quality cohort studies should be included in the evidence base. The study type combined with assessment of the methodological quality determines the level of evidence. In view of some methodological concerns in the Cochrane meta-analysis, particularly regarding definitions and diagnostic criteria for outcome measures and inclusion of non peer-reviewed studies/reports, a revision of the Cochrane analysis may seem warranted. Based on analysis of published peer-reviewed observational and interventional studies the results still indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is effective in the prevention of allergic diseases in high-risk infants, particularly in early infancy regarding food allergy and eczema. The most effective dietary regimen is exclusively breastfeeding for at least 4-6 months or, in absence of breast milk, formulas with documented reduced allergenicity for at least the first 4 months, combined with avoidance of solid food and cow's milk for the first 4 months.

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.