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.

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.

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.

Cystic degeneration and calcification following ischemic paralysis of the leg.

Increased pressure within a closed space which leads to a compromise of the circulation and function of tissues is referred to as a compartmental syndrome. The resulting changes range from the mild reversible ones to extensive necrosis and fibrosis. Rarely, a cystic calcified mass may develop in the affected area years after the onset of ischemia. Two such cases which involve the lower limb have been reported by Gallie. The authors report one new case of late cystic degeneration and calcification following ischemic paralysis of the leg.