Network meta-analysis of lorcaserin and oral hypoglycaemics for patients with type 2 diabetes mellitus and obesity.

In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments. Studies had to report ≥1 key outcome (change in weight or HbA1c, % HbA1c <7, hypoglycaemia). Direct meta-analysis was performed using DerSimonian and Laird random effects models, and network meta-analysis with Bayesian Markov-chain Monte Carlo random effects models; 6552 articles were screened and 41 included. Lorcaserin reduced weight significantly more than thiazolidinediones, glinides, sulphonylureas and dipeptidyl peptidase-4 inhibitors, some of which may have led to weight gain. There were no significant differences in weight change between lorcaserin and alpha-glucoside inhibitors, glucagon-like peptide-1 agonists and sodium/glucose cotransporter 2 inhibitors. Network meta-analysis showed lorcaserin was non-inferior to all other agents on HbA1c reduction and % achieving HbA1c of <7%. The risk of hypoglycaemia was not significantly different among studied agents except that sulphonylureas were associated with higher risk of hypoglycaemia than lorcaserin. Although additional studies are needed, this analysis suggests in a population of patients with a body mas index of ≥27 who do not achieve glycaemic control on a single agent, lorcaserin may be added as an alternative to an add-on glucose lowering medication.

Burden of skeletal-related events in prostate cancer: unmet need in pain improvement.

PURPOSE: Up to 75% of patients with prostate cancer experience metastatic bone disease, which leads to an increased risk for skeletal-related events (SREs) including pathological bone fracture, spinal cord compression, and hypercalcemia of malignancy. Our objective was to systematically review the literature on the impact of SREs on quality of life (QOL), morbidity, and survival with a primary focus on the impact of SREs on pain in prostate cancer patients. METHODS: We searched PubMed, limiting to peer-reviewed English-language human studies published in 2000-2010. The search was based on the US Food and Drug Administration and European Medicines Agency definition of an SRE, which includes pathologic fracture, spinal cord compression (SCC), hypercalcemia of malignancy, and radiotherapy or surgery to bone resulting from severe bone pain. RESULTS: A total of 209 articles were screened, of which 173 were excluded, and 36 were included in this review. Patients with SREs had more pain and worse survival compared with no SREs. Pathologic bone fractures worsened QOL and were associated with shorter survival. Radiation therapy of SCC alleviated pain and improved morbidity. SCC was associated with decreases in patient survival. Radiation therapy and surgery to bone improved pain. CONCLUSIONS: Specific SREs are associated with worse outcomes, including increased pain, poorer QOL, morbidity, and survival. Treatment of SREs is associated with improved pain, although there remains a need for more effective treatment of SREs in prostate cancer patients.

Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases.

The economic burden of acromegaly in the US has been largely unknown. We describe the prevalence of treatment patterns, complication rates, and associated healthcare utilization and costs of acromegaly in the US. Patients were identified between 1/1/2002 and 12/31/2009 in claims databases. During 1-year after each continuously-enrolled patient's first acromegaly claim, pharmacy and medical claims were used to estimate outcomes. Regression models were used to adjust outcomes. There were 2,171 acromegaly patients (mean age: 45.3 years; 49.7% female); 77.8% received the majority of their care from non-endocrinologists. Pharmacologic treatment was used by 30.8% of patients: octreotide-LAR in 18.6%, dopamine agonists in 9.8%, short-acting octreotide in 4.7%, pegvisomant in 4.1%, and lanreotide in 1.2%; 56% had biochemical monitoring. Comorbidities were common, ranging from 6.6% (colon neoplasms) to 25.6% (musculoskeletal abnormalities). Mean healthcare costs were $24,900. Adjusted analyses indicated comorbidities increased the odds of hospitalization: by 76% for musculoskeletal abnormalities; 193% for cardiovascular abnormalities; and 56% for sleep apnea (p < 0.05). Odds of emergency department visits increased by 87% (musculoskeletal) and 132% (cardiovascular abnormalities) (p < 0.01). After adjustments, colon neoplasms were associated with $8,401 mean increase in costs; musculoskeletal abnormalities with $7,502, cardiovascular abnormalities with $13,331, sleep apnea with $10,453, and hypopituitarism with $6,742 (p < 0.01). Complications are common and increase utilization and cost in acromegaly patients. Cardiovascular complications nearly tripled the odds of hospitalization (OR 2.93) and increased annual mean cost by $13,331. Adequate management of this disease may be able to reduce health care utilization and cost associated with these complications and with acromegaly in general.

Effect of the 12-gene colon cancer assay results on adjuvant treatment recommendations in patients with stage II colon cancer.

INTRODUCTION: The 12-gene colon cancer Recurrence Score assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. A survey was performed characterizing the assay's impact on treatment recommendations for these patients. METHODS: US medical oncologists (n = 346) who ordered the assay for ≥3 stage II colon cancer patients were asked to complete a web-based survey regarding their most recent such patient. Physicians surveyed represented users of the assay within the first 2 years of commercial availability which may include 'early adopters'. RESULTS: Most of 116 eligible physicians were in community practice (86%), with median 14.5 years' experience (range = 2-40). Mean patient age was 61 years (range = 32-85); 81% had T3 disease, and 38% had comorbidities. Of 76 patients tested for mismatch-repair/microsatellite-instability (MMR/MSI), 13 (17%) were MMR-deficient/MSI-high; 46 (61%) MMR-proficient/MSI-low; and 17 (22%) unknown. Most patients (84%) had ≥12 nodes examined. Median Recurrence Score result was 20 (range = 1-77). Before assay, treatment recommendations were specified for 92 (79%) patients, with no recommendation for 24 (21%). Of the 92 with pre-assay recommendations, chemotherapy was planned for 52 (57%) and observation for 40 (43%); the assay changed recommendations for 27 (29%). Treatment intensity decreased for 18 (67%) and increased for nine (33%) patients; it was more likely to decrease for lower Recurrence Score values and increase for higher values (p < 0.001). CONCLUSION: For stage II colon cancer patients receiving Recurrence Score testing, 29% of treatment recommendations were changed. Use of the assay may lead to reductions in treatment intensity. Study limitations include retrospective design, data gathering during the first 2 years of assay availability only, and potential non-representativeness of respondents.

Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy.

OBJECTIVE: To assess the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti-tumor necrosis factor therapy. METHODS: Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health-related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent-to-treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Short Form 36 (SF-36) was determined. RESULTS: Rituximab patients had statistically significantly greater pain relief. The FACIT-F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean +/- SD change from baseline for the SF-36 Physical Component Score was 6.64 +/- 8.74 for rituximab patients and 1.48 +/- 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF-36 Mental Component Score was 5.32 +/- 12.41 for rituximab patients and 2.25 +/- 12.23 for placebo patients (P = 0.0269). CONCLUSION: Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient-reported pain, fatigue, functional disability, health-related quality of life, and disease activity. These effects were sustained throughout the study.

Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding?

BACKGROUND: There is considerable worldwide confusion in the use of terminologies and definitions around the symptom of abnormal uterine bleeding (AUB), and these are leading increasingly to difficulties in setting up multinational clinical trials and in interpreting the results of studies undertaken in single centres. An international initiative was established to develop an agreement process to recommend clear, simple terminologies and definitions with the potential for wide acceptance. METHODS: After widespread consultation with relevant international and national organizations, journal editors and individuals, a modified Delphi process was developed to assess the current use of terminologies followed by a structured face-to-face meeting of 35 clinicians (mostly gynaecologists) and scientists in Washington. Focused small group discussions led to plenary assessment of concepts and recommendations using an electronic keypad voting system. RESULTS: There was almost universal agreement that poorly defined terms of classical origin used in differing ways in the English medical language should be discarded and that these should be replaced by simple, descriptive terms with clear definitions which have the potential to be understood by health professional and patient alike and which can be translated into most languages. The major recommendations were to replace terms such as menorrhagia, metrorrhagia, hypermenorrhoea and dysfunctional uterine bleeding. Suggestions for potentially suitable replacement terms and definitions are made. CONCLUSIONS: A simple terminology has been recommended for the description and definition of symptoms and signs of AUB. This manuscript should be a living document and should be part of an ongoing process with international medical and community debate. Classification of causes, investigations and cultural and quality of life issues should be part of the ongoing process.

Granulomatous infectious diseases associated with tumor necrosis factor antagonists.

The relationship between the use of tumor necrosis factor antagonists and onset of granulomatous infection was examined using data collected through the Adverse Event Reporting System of the US Food and Drug Administration for January 1998-September 2002. Granulomatous infections were reported at rates of approximately 239 per 100,000 patients who received infliximab and approximately 74 per 100,000 patients who received etanercept (P<.001). Tuberculosis was the most frequently reported disease, occurring in approximately 144 and approximately 35 per 100,000 infliximab-treated and etanercept-treated patients, respectively (P<.001). Candidiasis, coccidioidomycosis, histoplasmosis, listeriosis, nocardiosis, and infections due to nontuberculous mycobacteria were reported with significantly greater frequency among infliximab-treated patients. Seventy-two percent of these infection occurred < or =90 days after starting infliximab treatment, and 28% occurred after starting etanercept treatment (P<.001). These data indicate a risk of granulomatous infection that was 3.25-fold greater among patients who received infliximab than among those who received etanercept. The clustering of reports shortly after initiation of treatment with infliximab is consistent with reactivation of latent infection.

Evaluation of english and spanish health information on the internet

It provides information on the study of search engines performance, quality of health information on the internet, and readability assessment of health information on the internet.

Assessing symptoms before hysterectomy: is the medical record accurate?

OBJECTIVE: Our purpose was to evaluate the agreement between the documentation of symptoms leading to hysterectomy and the assessment of those symptoms by the patient. STUDY DESIGN: A retrospective study was performed of 497 women in southern California who had hysterectomies. Sensitivity, specificity, and kappa statistics were calculated for the medical records and were compared with patient interviews for the presence and severity of symptoms. RESULTS: The medical record was 93% sensitive and 61% specific for identifying bleeding and 79% sensitive and 55% specific for identifying pain. Overall agreement between physician records and patient interviews was moderate for bleeding (kappa, 0.55-0.58), fair for pain (kappa, 0.29-0.34), and poor for impairment as a result of bleeding or pain (kappa, 0.0-0.14). CONCLUSIONS: Physician overestimation of symptoms could lead to overuse of hysterectomy, whereas underestimation could result in underuse. Our results suggest that both underestimation and overestimation occur for patients with abnormal bleeding, pain, or both. If physicians accurately assess symptoms but fail to document them, examinations of appropriateness will be faulty unless patients are interviewed.

Health information on the Internet: accessibility, quality, and readability in English and Spanish.

CONTEXT: Despite the substantial amount of health-related information available on the Internet, little is known about the accessibility, quality, and reading grade level of that health information. OBJECTIVE: To evaluate health information on breast cancer, depression, obesity, and childhood asthma available through English- and Spanish-language search engines and Web sites. DESIGN AND SETTING: Three unique studies were performed from July 2000 through December 2000. Accessibility of 14 search engines was assessed using a structured search experiment. Quality of 25 health Web sites and content provided by 1 search engine was evaluated by 34 physicians using structured implicit review (interrater reliability >0.90). The reading grade level of text selected for structured implicit review was established using the Fry Readability Graph method. MAIN OUTCOME MEASURES: For the accessibility study, proportion of links leading to relevant content; for quality, coverage and accuracy of key clinical elements; and grade level reading formulas. RESULTS: Less than one quarter of the search engine's first pages of links led to relevant content (20% of English and 12% of Spanish). On average, 45% of the clinical elements on English- and 22% on Spanish-language Web sites were more than minimally covered and completely accurate and 24% of the clinical elements on English- and 53% on Spanish-language Web sites were not covered at all. All English and 86% of Spanish Web sites required high school level or greater reading ability. CONCLUSION: Accessing health information using search engines and simple search terms is not efficient. Coverage of key information on English- and Spanish-language Web sites is poor and inconsistent, although the accuracy of the information provided is generally good. High reading levels are required to comprehend Web-based health information.

Do longer postpartum stays reduce newborn readmissions? Analysis using instrumental variables.

OBJECTIVE: To determine the effect of postpartum length of stay on newborn readmission. DATA SOURCES: Secondary data set consisting of newborns born in Washington state in 1989 and 1990. The data set contains information about the characteristics of the newborn and its parents, physician, hospital, and insurance status. STUDY DESIGN: Analysis of the effect of length of stay on the probability of newborn readmission using hour of birth and method of delivery as instrumental variables (IVs) to account for unobserved heterogeneity. Of approximately 150,000 newborns born in Washington in 1989 and 1990, 108,551 (72 percent) were included in our analysis. PRINCIPAL FINDINGS: Newborns with different lengths of stay differ in unmeasured characteristics, biasing estimates based on standard statistical methods. The results of our analyses show that a 12-hour increase in length of stay is associated with a reduction in the newborn readmission rate of 0.6 percentage points. This is twice as large as the estimate obtained using standard statistical (non-IV) methods. CONCLUSION: An increase in the length of postpartum hospital stays may result in a decline in newborn readmissions. The magnitude of this decline in readmissions may be larger than previously thought.

Infant mortality and early postpartum discharge.

OBJECTIVE: To assess additional risk of newborn death owing to early discharge. METHODS: This was a historical cohort study using Washington State linked birth certificates, death certificates, and hospital discharge records that covered 47,879 live births in 1989 and 1990. Logistic regression was used to assess risk of death within the first year of life after early discharge (less than 30 hours after birth) compared with later discharge (30-78 hours after birth). RESULTS: Newborns discharged early were more likely to die within 28 days of birth (odds ratio [OR] 3.65; 95% confidence interval [CI] 1.56, 8.54), between 29 days and 1 year (OR 1.61; 95% CI 1.10, 2.36), and any time within the first year (OR 1.84; 95% CI, 1.31, 2.60) of life than newborns sent home later. Newborns discharged early also were more likely to die of heart-related problems (OR 3.72; CI 1.25, 11.04) and infections (OR 4.72; CI 1.13, 19.67) within 1 year of birth than newborns discharged later. CONCLUSION: Newborns discharged within 30 hours of birth are at increased risk of death within the first year of life.

An agenda for research into uterine artery embolization: results of an expert panel conference.

PURPOSE: To develop a research agenda for uterine artery embolization (UAE) for the treatment of symptomatic leiomyomata. MATERIALS AND METHODS: An expert panel was convened to examine data and develop a consensus for UAE research. Panelists reviewed data from articles about UAE and data on hysterectomy and myomectomy, which were abstracted into evidence tables. A modified Delphi process was used to rate the importance of measuring specific outcomes and a nominal group process was used to develop ideas for study designs. RESULTS: Panelists agreed that UAE studies would have to examine certain key measures. Outcomes identified as either "important to measure" or "essential to measure" were death, reoperation, operative injury, menorrhagia, premature menopause, recurrence of myomata, and satisfaction. The panel proposed four areas for research: randomized trial, prospective registry, disease-specific quality-of-life instrument, and cost analysis. CONCLUSIONS: Symptomatic uterine leiomyomata are a major health concern for women. New techniques that promise to provide symptom relief deserve careful consideration. Traditionally, surgical procedures have been poorly studied until after they have been widely used. If the process described in this article can guide the acquisition of knowledge in this field, it may serve as a model for evaluating other new technologies before they become widely adopted.

The appropriateness of recommendations for hysterectomy.

OBJECTIVE: To evaluate the appropriateness of recommendations for hysterectomies done for nonemergency and non-oncologic indications. METHODS: We assessed the appropriateness of recommendations for hysterectomy for 497 women who had the operation between August 1993 and July 1995 in one of nine capitated medical groups in Southern California. Appropriateness was assessed using two sets of criteria, the first developed by a multispecialty expert physician panel using the RAND/University of California-Los Angeles appropriateness method, and the second consisting of the ACOG criteria sets for hysterectomies. The main outcome measure was the appropriateness of recommendation for hysterectomy, based on expert panel ratings and ACOG criteria sets. RESULTS: The most common indications for hysterectomy were leiomyomata (60% of hysterectomies), pelvic relaxation (11%), pain (9%), and bleeding (8%). Three hundred sixty-seven (70%) of the hysterectomies did not meet the level of care recommended by the expert panel and were judged to be recommended inappropriately. ACOG criteria sets were applicable to 71 women, and 54 (76%) did not meet ACOG criteria for hysterectomy. The most common reasons recommendations for hysterectomies considered inappropriate were lack of adequate diagnostic evaluation and failure to try alternative treatments before hysterectomy. CONCLUSION: Hysterectomy is often recommended for indications judged inappropriate. Patients and physicians should work together to ensure that proper diagnostic evaluation has been done and appropriate treatments considered before hysterectomy is recommended.

A controlled trial of intravenous immune globulin for the prevention of serious infections in adults with advanced human immunodeficiency virus infection.

BACKGROUND: Studies on human immunodeficiency virus-infected children suggest that high-dose immune globulin therapy might be beneficial in reducing the episodes of recurrent infections. In adults, comparable studies are not available. OBJECTIVE: To determine the efficacy of intravenous (IV) immune globulin therapy in preventing infections and reducing days with fever, as well as the duration and frequency of hospitalization for human immunodeficiency virus-infected adults, in a prospective, randomized outpatient clinical trial. METHODS: Adult patients who met Centers for Disease Control and Prevention criteria B and C were randomized to be treated with (n = 70) or without (n = 57) IV immune globulin. Patients who were assigned to treatment with IV immune globulin received 400 and 200 mg/kg of this drug initially and every 21 days thereafter, respectively. Primary end points were the occurrence of laboratory-proved or clinically diagnosed infections and death caused by infection. RESULTS: In comparison with patients in the control group, IV immune globulin treatment significantly increased the time for which the patients who met Centers for Disease Control and Prevention criteria B and C were free from serious infection (P < .001). Twelve (17%) of the patients who received IV immune globulin had infection-related deaths compared with 20 (35%) of the control patients; however, this was not statistically significant (P = .06). Furthermore, immune globulin treatment was associated with an overall reduction in the number and duration of hospitalizations for short-term care (P = .002), days with fever (P < .001), and frequency of diarrhea (P < .001). Because of these results, the study was stopped by the local ethical board. CONCLUSION: Prophylactic IV immune globulin treatment in human immunodeficiency virus-infected adults decreases the frequency of serious infections and is associated with a reduction of hospitalization for short-term care.

Feedback from chief residents about proposed revisions of the special requirements for internal medicine residencies.

PURPOSE: To receive feedback from chief medical residents about what they and their residents would think of proposed revisions of the Special Requirements for Residency Programs in Internal Medicine. METHOD: A 71-item questionnaire was mailed in the fall of 1991 to a chief resident at each of 426 U.S. internal medicine residencies. A five-point Likert scale, ranging from 1 (strongly agree) to 5 (strongly disagree), was used. In addition, the chief residents were asked for qualitative comments. The chief residents were requested to reflect residents' opinions when completing the questionnaire. RESULTS: 272 (64%) of the questionnaires were returned. The mean rating for all questions was 2.12, SD, 0.66. The 12 changes most strongly supported (means < or = 1-1.46) included enhanced training in interviewing, communication, and interpersonal skills and in physical examination skills; emphasis on residency as an educational experience and on general internal medicine in the design of core lectures and ambulatory care clinics; and a requirement for written parental leave policies. Areas of moderate to less strong agreement included requirements for faculty and resident research, and that residents report moonlighting experiences to their program directors. CONCLUSION: The chief residents supported most of the proposed revisions of the Special Requirements, including a new proposal for enhancing professionalism in residency. The data reinforce the need to make residency education consonant with the practice of medicine and the changing demographics of the profession as well as to address resident indebtedness.