Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial.

OBJECTIVES: To study the efficacy and safety of fasinumab in moderate-to-severe, chronic low back pain (CLBP). METHODS: In this phase II/III, double-blind, placebo-controlled study, patients with CLBP aged ≥35 years with inadequate pain relief/intolerance to acetaminophen, non-steroidal anti-inflammatory drugs and opioids were randomised to fasinumab 6 or 9 mg subcutaneous every 4 weeks (Q4W), 9 mg intravenous every 8 weeks (Q8W) or placebo. Primary endpoint was change from baseline to week 16 in average daily low back pain intensity (LBPI) numeric rating score. Key secondary efficacy variables included Roland-Morris Disability Questionnaire (RMDQ) and Patient Global Assessment (PGA). The results are based on a modified intent-to-treat analysis of 563/800 planned patients when enrolment was stopped early given emerging signals of joint risk in other osteoarthritis (OA) studies at doses being tested here. RESULTS: Significant placebo-adjusted LBPI reductions at week 16 were observed for fasinumab 9 mg Q4W and Q8W (least squares mean (standard error) -0.7 (0.3); both nominal p<0.05), but not 6 mg (-0.3 (0.3); p=0.39). RMDQ and PGA improvements to week 16 were greatest for fasinumab 9 mg intravenous. Numerically greater efficacy occurred in patients with, versus those without, peripheral OA (pOA) over 16 weeks. Treatment-emergent adverse events (AEs) occurred in 274/418 (65.6%) patients in the combined fasinumab groups and 94/140 (67.1%) placebo patients. Joint AEs, mostly rapid progressive OA type 1, were more frequent in the combined fasinumab groups (19 events in 16 patients (3.8%) vs 1 event in 1 patient (0.7%) for placebo); all except one occurred in pOA patients. CONCLUSIONS: Fasinumab highest doses, but not lower dose, improved both CLBP pain and function. Most joint AEs occurred in pOA patients, consistent with earlier findings in symptomatic OA. Further study is needed of patients with CLBP with and without pOA to determine optimal benefit-risk.

Racial/ethnic disparities in contraceptive use: variation by age and women's reproductive experiences.

OBJECTIVE: Disparities in unintended pregnancy in the United States are related, in part, to black and Hispanic women being overall less likely to use effective contraceptive methods. However, the fact that these same groups are more likely to use female sterilization, a highly effective method, suggests there may be variability in disparities in contraceptive use across a woman's life course. We sought to assess the relationship between race/ethnicity and contraceptive use in a nationally representative sample and to approximate a life course perspective by examining effect modification on these disparities by women's age, parity, and history of unintended pregnancy. STUDY DESIGN: We conducted an analysis of the 2006 through 2010 National Survey of Family Growth to determine the association between race/ethnicity and: (1) use of any method; (2) use of a highly or moderately effective method among women using contraception; and (3) use of a highly effective method among women using contraception. We then performed analyses to assess interactions between race/ethnicity and age, parity, and history of unintended pregnancy. RESULTS: Our sample included 7214 females aged 15-44 years. Compared to whites, blacks were less likely to use any contraceptive method (adjusted odds ratio, 0.65); and blacks and Hispanics were less likely to use a highly or moderately effective method (adjusted odds ratio, 0.49 and 0.57, respectively). Interaction analyses revealed that racial/ethnic disparities in contraceptive use varied by women's age, with younger women having more prominent disparities. CONCLUSION: Interventions designed to address disparities in unintended pregnancy should focus on improving contraceptive use among younger women.

Prospective evaluation of a clinical pathway for suspected appendicitis.

OBJECTIVE: To evaluate the diagnostic accuracy of a clinical pathway for suspected appendicitis combining the Samuel's pediatric appendicitis score (PAS) and selective use of ultrasonography (US) as the primary imaging modality. METHODS: Prospective, observational cohort study conducted at an urban, academic pediatric emergency department. After initial evaluation, patients were determined to be at low (PAS 1-3), intermediate (PAS 4-7), or high (PAS 8-10) risk for appendicitis. Low-risk patients were discharged with telephone follow-up. High-risk patients received immediate surgical consultation. Patients at intermediate risk for appendicitis underwent US. RESULTS: Of the 196 patients enrolled, 65 (33.2%) had appendicitis. An initial PAS of 1-3 was noted in 44 (22.4%), 4-7 in 119 (60.7%), and 8-10 in 33 (16.9%) patients. Ultrasonography was performed in 128 (65.3%) patients, and 48 (37.5%) were positive. An abdominal computed tomography scan was requested by the surgical consultants in 13 (6.6%) patients. The negative appendectomy rate was 3 of 68 (4.4%). Follow-up was established on 190 of 196 (96.9%) patients. Overall diagnostic accuracy of the pathway was 94% (95% confidence interval [CI] 91%-97%) with a sensitivity of 92.3% (95% CI 83.0%-97.5%), specificity of 94.7% (95% CI 89.3%-97.8%), likelihood ratio (+) 17.3 (95% CI 8.4-35.6) and likelihood ratio (-) 0.08 (95% CI 0.04-0.19). CONCLUSIONS: Our protocol demonstrates high sensitivity and specificity for diagnosis of appendicitis in children. Institutions should consider investing in resources that increase the availability of expertise in pediatric US. Standardization of care may decrease radiation exposure associated with use of computed tomography scans.

Depressive symptomatology, quality of life and disease control among individuals with well-characterized severe asthma.

OBJECTIVES: A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well-characterized cohort of asthmatics and healthy controls. METHODS: Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation and rescue medication use. RESULTS: Individuals with asthma (n = 91) reported more symptoms of depression than controls (n = 36; p < 0.001). Those with severe asthma (n = 49) reported more symptoms of depression (p = 0.002) and poorer asthma control (p < 0.0001) than those with not severe asthma. Worse asthma control was associated with more depressive symptoms in severe (r = 0.46, p = 0.002) but not in not severe (r = 0.13, p = 0.40) asthmatics. The relationship of symptoms of depression among severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. CONCLUSIONS: Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life.

Does a history of unintended pregnancy lessen the likelihood of desire for sterilization reversal?

BACKGROUND: Unintended pregnancy has been significantly associated with subsequent female sterilization. Whether women who are sterilized after experiencing an unintended pregnancy are less likely to express desire for sterilization reversal is unknown. METHODS: This study used national, cross-sectional data collected by the 2006-2010 National Survey of Family Growth. The study sample included women ages 15-44 who were surgically sterile from a tubal sterilization at the time of interview. Multivariable logistic regression was used to examine the relationship between a history of unintended pregnancy and desire for sterilization reversal while controlling for potential confounders. RESULTS: In this nationally representative sample of 1,418 women who were sterile from a tubal sterilization, 78% had a history of at least one unintended pregnancy and 28% expressed a desire to have their sterilization reversed. In unadjusted analysis, having a prior unintended pregnancy was associated with higher odds of expressing desire for sterilization reversal (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.15-2.79). In adjusted analysis controlling for sociodemographic factors, unintended pregnancy was no longer significantly associated with desire for reversal (OR: 1.46; 95% CI: 0.91-2.34). CONCLUSION: Among women who had undergone tubal sterilization, a prior history of unintended pregnancy did not decrease desire for sterilization reversal.

A comparison of the E-BEHAVE-AD, NBRS, and NPI in quantifying clinical improvement in the treatment of agitation and psychosis associated with dementia.

OBJECTIVES: The aim of this study is to compare the Empirical Behavioral Rating Scale (E-BEHAVE-AD), Neurobehavioral Rating Scale (NBRS), and Neuropsychiatric Interview (NPI) in detecting behavioral disturbance and psychotic symptoms in dementia and characterizing changes in response to treatment. DESIGN: Eighty-seven subjects in the randomized controlled trial "Continuation Pharmacotherapy for Agitation of Dementia" were included in this analysis. We compared the detection in, and changes of, both agitation and psychosis, using these three instruments. A receiver operating characteristic analysis was performed to compare the performance of the three instruments in detecting global improvement. RESULTS: The instruments were equally likely to detect agitation. The NBRS was most likely to detect psychosis. Although the NPI best detected improvement in agitation, the instruments were equal for detecting improvement in psychosis. In the receiver operating characteristic analysis for overall clinical improvement in response to treatment, there were no differences in the areas under the correlated curves for the three instruments, but they demonstrated different sensitivity and specificity at different cutoff points for target symptom reduction. The E-BEHAVE-AD performed best at a cut point of 30% target symptom reduction and the NBRS and NPI both performed best at 50%. CONCLUSION: The E-BEHAVE-AD, NBRS, and NPI were more similar than different in characterizing symptoms but differed in detecting response to treatment. Differences in sensitivity and specificity may lead clinicians to prefer a specific instrument, depending on their goal and the expected magnitude of response to any specific intervention.

Acupuncture for the treatment of major depressive disorder: a randomized controlled trial.

BACKGROUND: Over 50% of patients with major depressive disorder (MDD) either do not tolerate or do not respond to antidepressant medications. Several preliminary studies have shown the benefits of acupuncture in the treatment of depression. We sought to determine whether a 2-point electroacupuncture protocol (verum acupuncture) would be beneficial for MDD, in comparison to needling at nonchannel scalp points with sham electrostimulation (control acupuncture). METHOD: Fifty-three subjects aged 18-80 years, recruited via advertisement or referral, were included in the primary analysis of our randomized controlled trial, which was conducted from March 2004 through May 2007 at UPMC Shadyside, Center for Complementary Medicine, in Pittsburgh, Pennsylvania. Inclusion criteria were mild or moderate MDD (according to the Structured Clinical Interview for DSM-IV Axis I Disorders) and a score of 14 or higher on the Hamilton Depression Rating Scale (HDRS). Exclusion criteria included severe MDD, seizure disorder or risk for seizure disorder, psychosis, bipolar disorder, chronic MDD, treatment-resistent MDD, and history of substance abuse in the prior 6 months. Patients were randomized to receive twelve 30-minute sessions of verum versus control acupuncture over 6 to 8 weeks. The HDRS was the primary outcome measure. The UKU Side Effect Rating Scale was used to assess for adverse effects. RESULTS: Twenty-eight subjects were randomized to verum electroacupuncture and 25 to control acupuncture. The 2 groups did not differ with regard to gender, age, or baseline severity of depression. Both groups improved, with mean (SD) absolute HDRS score decreases of -6.6 (5.9) in the verum group and -7.6 (6.6) in the control group, corresponding to 37.5% and 41.3% relative decreases from baseline. There were no serious adverse events associated with either intervention, and endorsement of adverse effects was similar in the 2 groups. CONCLUSIONS: We were unable to demonstrate a specific effect of electroacupuncture. Electroacupuncture and control acupuncture were equally well tolerated, and both resulted in similar absolute and relative improvement in depressive symptoms as measured by the HDRS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00071110.