Cohort study: Neurological and cognitive-behavioral sequelae of acquired Zika virus infection among Nicaraguan children.

BACKGROUND: ZIKV has neuroinvasive properties, and in utero exposure can cause birth defects, but little is known about the neurological and neurocognitive impacts of acquired ZIKV infection, particularly in children. METHODS: We assessed neurological symptoms frequency among ZIKV-infected children within one year after ZIKV infection. Three to 5 years post-infection, these children and a matched group of uninfected children were assessed via questionnaires, neurological exams, and neuropsychological testing to evaluate the association between prior ZIKV infection and subsequent neurological symptoms, and cognitive-behavioral function. RESULTS: Among 194 ZIKV-infected children, 3 reported asthenia, 4 reported neck pain, and 10 reported back pain within one year post-infection. At follow-up, clinician-observed cranial nerve abnormalities were significantly more common among ZIKV-infected vs. uninfected children (16 vs. 3; p < 0.01), with vestibulocochlear nerve abnormalities observed most frequently. While ZIKV-infected children scored better than uninfected on cognitive measures, this difference was not clinically meaningful. CONCLUSIONS: Neurological signs, including paresthesia and cranial nerve abnormalities, were observed among ZIKV-infected participants in our study. However, we did not observe a meaningful link between acquired ZIKV infection and subsequent neurological, cognitive, or behavioral outcomes in a representative sample. An exception may be hearing impairment and loss, which should be explored further in future studies. IMPACT: Neurological symptoms, though rare, were observed and reported more frequently among ZIKV-infected vs. uninfected children. These included: asthenia, neck pain, back pain, paresthesia, and cranial nerve abnormalities. Neurocognitive and behavioral test scores were similar among ZIKV-infected and uninfected children. Our study suggests that ZIKV-infected children should be monitored for neurological symptoms and cranial neuropathy to better understand the full burden of acquired ZIKV infection among children.

School Readiness Among United States Children: Results From the 2022 National Survey of Children's Health.

OBJECTIVE: Provide the latest national and state estimates and correlates of the proportion of young children who are healthy and ready to learn (HRTL) using a revised measure from the National Survey of Children's Health (NSCH). METHODS: Data were analyzed for 11,121 children ages 3 to 5 years from the 2022 NSCH, an address-based, parent-completed survey on the health and well-being of children in the United States. A total of 27 items across 5 domains (early learning skills, social emotional development, self-regulation, motor development, and health) were used to calculate domain-specific assessments scored as "on track," "emerging," or "needs support" according to age-appropriate developmental expectations. Children "on track" in 4 to 5 domains with no domain that "needs support" were considered HRTL. RESULTS: In 2022, 63.6% of 3- to 5-year-old children were HRTL. The proportion of children "on track" ranged from just over two thirds for early learning skills and motor development to 88.9% for health. One million children, or 9.0%, needed support in multiple domains. Being HRTL was associated with child, family, community factors including participation in early childhood education, special health care needs status/type, male sex, reading/singing/storytelling by family members, adverse childhood experiences, parental mental health and education, food insufficiency, outdoor play, household language, neighborhood amenities, rural residence, medical home access. CONCLUSIONS: Nearly two thirds of young children are reported to be HRTL, meeting the Title V National Outcome Measure for School Readiness. Using a revised measure, modifiable factors are identified which offer a range of intervention opportunities at the child, family, and community levels.

Integrating Maternal Depression Screening Into an Early Intervention Program: An Implementation Evaluation.

BACKGROUND: In all 50 states, early intervention (EI) services to improve long-term child cognitive and academic outcomes are provided to infants and toddlers with suspected or diagnosed developmental delays. When mothers of EI-enrolled children experience depressive symptoms, uptake of EI services can be compromised. AIMS: The purpose of the article is to present a depressive symptom screening intervention for mothers consisting of toolkit development for EI staff and families, symptom screening for mothers and follow-up protocol. To formally evaluate the implementation of the intervention, our research team followed the consolidated framework for implementation research (CFIR). METHODS: Participants were 12 EI service coordinators across two offices. Focus groups and individual interviews were used to develop the toolkit and education module. Through the five CFIR domains, we evaluated the implemented intervention in order to allow other teams to learn from our experiences. RESULTS: Our team successfully partnered with SCs to develop the intended deliverables. Still, the SCs found it challenging to conduct the screenings and reported mixed success. CONCLUSIONS: Preparation of EI SCs to integrate mental health screenings into their existing skillsets requires a high level of support from the research team, resulting in a rich understanding of the barriers-and potential rewards-for staff and families.

Incorporating callous-unemotional behaviors into school-based research.

This study investigated the utility of including teacher-reported callous-unemotional (CU) behaviors in the assessment of disruptive behaviors in school-based research. Participants included 138 first- and second-grade children (68% male; 76% eligible for free or reduced-price lunch; 61% Black, 9% Latinx, 23% White, and 7% multiracial) who completed assessments during the baseline assessment of an intervention study. Results indicated that teachers could distinguish CU from traditional indicators of disruptive behavior, including attention deficit hyperactivity disorder (ADHD) behaviors and conduct problems (CP). When considered alone, there was mixed evidence for the utility of CU behaviors. Although higher levels of CU behaviors explained unique variation in teacher-reported social competence and global impairment, CU behaviors did not explain unique variation in disciplinary infractions, classroom behavior, or academic functioning after accounting for ADHD and CP behaviors. A different pattern of results was evident when CU was considered in conjunction with ADHD and CP behaviors. Latent profile analyses identified three subgroups of participants (i.e., a nondisruptive group, an ADHD group, and a comorbid group, who exhibited elevated levels of ADHD, CP, and CU). Compared to the nondisruptive group, the ADHD group exhibited higher rates of off-task classroom behavior and worse academic functioning. The comorbid group exhibited moderate-to-large differences from both groups on teacher-reported and objective outcomes. The implications of these results are discussed with respect to the potential value of incorporating CU behaviors, which are becoming prominent in clinical psychology and psychiatry, into school-based research and for school psychology practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Health Care Utilization for Privately and Publicly Insured Children During Autism Insurance Reform.

We examined the effects of insurance type on health service utilization among children with autism spectrum disorder (ASD) following autism insurance reform by analyzing the most recent data from the 2019 National Survey of Children's Health. Families with private insurance were less likely to report that their health insurance covered needed services compared to families with public insurance. Privately versus publicly insured children were not significantly different in receiving behavioral or medication treatment, or in parental frustration in efforts to obtain services. However, parents' frustration escalated with increased ASD severity. Findings from this study suggest the need for continuing to improve implementation of health insurance reform legislation and providing adequate ASD-related services for children with private insurance.

Forearm bone mineral density and fracture incidence in postmenopausal women with osteoporosis: results from the ACTIVExtend phase 3 trial.

Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. INTRODUCTION: Abaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend. METHODS: Ultradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method. RESULTS: At cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs - 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant). CONCLUSION: Ultradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01657162 submitted July 31, 2012.

A logic model for educator-level intervention research to reduce racial disparities in student suspension and expulsion.

Disproportionate rates of suspension and expulsion, evident from early childhood, for students of color relative to White peers are a significant racial equity issue in the U.S. education system, with far-reaching effects. In this article, we present a logic model for educator-level interventions that have the potential to reduce disparate discipline practices and ultimately work toward a more equitable school climate. We describe how an integrated approach to supporting all children's constitutional right to a free public education, which is prevented by exclusionary discipline practices, must purposefully integrate social and emotional learning, classroom management, cultural competence, and racial equity approaches that target educators. Together, the integration of these approaches has the potential to impact initial, intermediate, and long-term education outcomes by enhancing educators' practices and raising awareness of their internal and interpersonal biases and role in perpetuating institutional racism in education. We conclude with recommendations for how this logic model can be used to guide future research to further our knowledge in this area to support educators in their practice and inform educational policy. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Multimodal Approach of Pulmonary Artery Intimal Sarcoma: A Single-Institution Experience.

INTRODUCTION: Pulmonary artery sarcoma (PAS) is a rare tumor, whose therapeutic approach is mainly based on surgery, either pneumonectomy or pulmonary endarterectomy (PEA). The prognosis reported in published series is very poor, with survival of 1.5 months without any kind of treatment. PATIENTS AND METHODS: From January 2010 to January 2016, 1027 patients were referred to our hospital for symptoms of acute or chronic pulmonary thromboembolic disease. Twelve patients having a confirmed diagnosis of PAS underwent PEA. Median age was 64.5 years. Most patients had a long history of symptoms, having a median time of 7.5 months from onset of symptoms to surgery. RESULTS: Following PEA and cardiopulmonary rehabilitation, 10 patients received conventional chemotherapy with doxorubicin and ifosfamide, starting at a median of 42 days from surgery. Four patients also received radiotherapy. Four patients have died due to disease progression, while 7 are still alive, with 5 being disease-free at 4-55+ months from diagnosis. CONCLUSIONS: In patients with PAS, a multimodal approach including PEA, CT, and RT is feasible but it should be evaluated individually, according to the tumor extension and the patient's clinical condition. Apart from improving quality of life mainly by reducing or delaying symptoms due to PH, it may improve life expectancy.

Sex differences in the outcome of juvenile social isolation on HPA axis function in rats.

Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot-shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine reactivity to stress, plasticity and emotionality in a sexually dimorphic manner.

Inter-observer agreement for the evaluation of bone involvement on Whole Body Low Dose Computed Tomography (WBLDCT) in Multiple Myeloma (MM).

OBJECTIVE: We aimed to assess inter-observer agreement in bone involvement evaluation and define accuracy and reproducibility of MDCT images analysis in Multiple Myeloma (MM), by comparing two acquisition protocols at two different institutions. METHODS: A total of 100 MM patients underwent whole body low-dose computed tomography (WB-LDCT), with two protocols: Group I (50 patients), 80 kV and 200-230 mAs; Group II, 120 kV-40 mAs. Four readers (two experts) retrospectively reviewed 22 anatomical districts, reporting the following for each patient: 1) osteolytic lesions; 2) cortical bone integrity; 3) fractures; 4) risk of vertebral collapse; 5) hyperattenuating bone lesions; and 6) extraosseous extension. Inter-observer agreement (by all readers, expert and young observers and comparison of the two protocols) was then statistically analyzed. RESULTS: According to Cohen's criteria, inter-observer agreement among the four readers and between experts and residents was good for the detection of bone lesions and extra-medullary extension, and for the evaluation of risk of collapse and cortical integrity. There was good agreement when comparing the two protocols. A greater variability was found for the evaluation of hyperattenuating lesions and the presence of fractures. CONCLUSIONS: WB-LDCT represents a reproducible and reliable technique that is helpful for defining bone disease in MM patients, with partial influence of readers' experience. KEY POINTS: • MDCT represents a reproducible technique for defining bone disease in MM. • Overall inter-observer agreement is good, even when comparing two different protocols. • Influence of readers' experience on image analysis is partial.

Examining the validity of the family investment and stress models and relationship to children's school readiness across five cultural groups.

Using the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) dataset, this study examined whether the family investment and the family stress models generalized to non-European American (EA) families. Specifically, we examined whether parenting processes mediated the association between family demographics and children's school readiness, and whether the pathways vary across cultural groups. Both models were most salient for EAs followed by African Americans (AAs) and Spanish-speaking Hispanics, but less so for English-speaking Hispanics (EHs) and Asian Americans. Findings indicated that sensitive parenting was a salient mediator between family demographics and children's school readiness for all groups except EHs; negative parenting and parent-child activities were salient mediators for EAs only.

Radiofrequency ablation of metastatic lesions from breast cancer.

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women. Various studies [5,6] have shown that surgical resection of single liver or lung metastases in patients with metastases from BC increases survival. Radiofrequency ablation (RFA) can be an alternative to resection in some patients when resection is not feasible. MATERIALS AND METHODS: From January 2002 to December 2008, 491 patients with liver metastases underwent US-guided percutaneous RFA. Of these patients 5 (5/491; 1%) had BC. In the same period, 32 patients with pulmonary metastases underwent CT-guided RFA. Of these patients 3 (3/32; 9%) had BC. Mean age was 61.3 years. All patients were postmenopausal and receiving polychemotherapy according to international guidelines. Inclusion criteria for RFA treatment of metastases from BC applied are identical or in some cases more restrictive than those reported in the literature. RESULTS: There were no deaths or severe complications and no treatment failures. Disease free and overall median survival were respectively 7.65 and 25.7 months after US-guided RFA and 13.4 and 34.8 months after CT-guided RFA. During follow-up (mean follow-up 26 months, range 4-63 months) 5/8 (62.5%) patients exhibited recurrence: 3/5 (60%) had local recurrence and 2/5 (40%) had non-local recurrence; 4/5 patients with recurrence were re-treated. DISCUSSION: The authors' experience confirms that RFA is an effective, safe and repeatable technique in the treatment of metastases from BC. Metastatic recurrence rate confirms that metastatic BC is a disease which requires a multidisciplinary approach and that the role of chemotherapy is indisputable. Effects on survival are promising but further confirmation is needed through prospective randomized studies.

Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients.

OBJECTIVE: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores. METHODS: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months). RESULTS: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores. CONCLUSION: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

Pulmonary eosinophilic infiltrates.

Pulmonary eosinophilic infiltrates include an heterogeneous group of disorders characterized by the presence of eosinophils in the lungs as detected by bronchoalveolar lavage or tissue biopsy, with or without blood eosinophilia. The disease can be idiopathic (simple pulmonary eosinophilia, acute and chronic eosinophilic pneumonia, hypereosinophilic syndrome), secondary (to drugs, parasites, fungal and mycobacterial infection, irradiation, toxic products) or associated with diffuse lung diseases (connective tissue diseases and some neoplasms). Pathologists faced with eosinophils in the lungs (either on cytology or biopsy) should keep in mind several possibilities, although a diagnosis of certainty is rarely based on morphology alone. Correlation with laboratory tests, imaging studies and clinical presentation has a key role, even if some pulmonary eosinophilic diseases are sufficiently characteristic on clinico-radiologic ground to not require a biopsy (e.g. some drug reactions, parasitic infections, idiopathic hypereosinophilic syndrome, allergic bronchopulmonary aspergillosis). Nevertheless, pathologists can play a central role because they can be the first to note eosinophils in the lungs of a very sick patient. Knowledge of histologic features and a striking collaboration with other physicians are necessary to achieve correct diagnosis and to establish adequate treatments.

Parental engagement and barriers to participation in a community-based preventive intervention.

This study examined parent characteristics and barriers to participation in a community-based preventive intervention with a sample of 201 parents from low-income and predominantly ethnic minority backgrounds. Person-centered analyses revealed five subgroups of parents who demonstrated variability in their parent characteristics, which included psychological resources and level of parental involvement in education. Group membership was associated with differences in school involvement and use of the psychoeducational intervention at home, after accounting for the number of barriers to engagement. For the intervention attendance variable, greater number of barriers was associated with decreased attendance only for parents in the resilient subgroup and the psychologically distressed subgroup. Attendance remained constant across levels of barriers for the other three subgroups of parents. The results of the study inform theory and practice regarding how to tailor preventive interventions to accommodate subgroups of parents within populations that experience barriers to accessing mental health services.

Enhancement and safety of iomeprol-400 and iodixanol-320 in patients undergoing abdominal multidetector CT.

The purpose of this study was to compare iomeprol-400 and iodixanol-320 for contrast enhancement and safety in patients undergoing liver multidetector CT (MDCT). 183 patients undergoing MDCT received equi-iodine (40 gI) iomeprol-400 (n = 91) or iodixanol-320 (n = 92) IV at 4 ml s(-1). Two off-site, independent, blinded readers determined the contrast density (in Hounsfield units (HUs)) in the abdominal aorta, inferior vena cava, portal vein and liver parenchyma during the arterial and portal phases. The mean contrast densities achieved were compared and 95% confidence intervals (CIs) estimated. Heart rate was measured at baseline and at post-dose peak, and a full safety assessment was performed. Study group demographics were comparable. Iomeprol-400 produced significantly greater enhancement of the aorta during the arterial phase (Reader 1: 337.3 HU vs 294.9 HU, 95% CI of difference (19.4, 65.5), p = 0.0004; Reader 2: 325.7 HU vs 295.3 HU, 95% CI of difference (6.6, 54.3), p = 0.01) and greater enhancement of the liver parenchyma during the portal venous phase (Reader 1: 115.1 H vs 108.6 HU, 95% CI of difference (0.27, 12.7), p = 0.04; Reader 2: 115.2 H vs 109.3 HU, 95% CI of difference (-0.1, 11.8), p = 0.05). Similar enhancement of the inferior vena cava and portal vein was noted. Comparably negligible increases in the mean heart rate were observed. Adverse events occurred in 1/91 (1.1%) subjects after iomeprol-400 and 4/92 (4.3%) subjects after iodixanol-320. In conclusion, iomeprol-400 produces greater arterial and portal phase enhancement and has a similarly negligible impact on heart rate and safety.

Psychosocial treatments for preschool-aged children with Attention-Deficit Hyperactivity Disorder.

This article reviews the research literature on psychosocial treatments for preschool-aged children with Attention-Deficit Hyperactivity Disorder (ADHD) in the context of the developmental and contextual needs of this population (e.g., increased parenting demands, differences in classroom structure, and the child's emerging developmental capacities). Discussion of the findings and limitations of existing studies is provided for parent-training approaches, classroom management strategies, and multimodal treatments. Although the empirical base is quite small for ADHD-specific samples, parent-training interventions have the greatest overall support for improving behavioral outcomes, with a variety of different approaches having shown effectiveness. Very few studies of classroom management and multimodal interventions have been conducted in this age group; however, initial data show promising results for teacher training and consultation interventions. The body of research suggests that the most effective treatments for clinical samples of preschoolers with ADHD and their families may be individually delivered, developmentally appropriate, and multimodal.

Gastrointestinal tolerability of etoricoxib in rheumatoid arthritis patients: results of the etoricoxib vs diclofenac sodium gastrointestinal tolerability and effectiveness trial (EDGE-II).

OBJECTIVE: A randomised, double-blind study to compare the gastrointestinal (GI) tolerability, safety and efficacy of etoricoxib and diclofenac in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 4086 patients (mean age 60.8 years) diagnosed with RA were enrolled and received etoricoxib 90 mg daily (n = 2032) or diclofenac 75 mg twice daily (n = 2054). Use of gastroprotective agents and low-dose aspirin was allowed. The prespecified primary end point consisted of the cumulative rate of patient discontinuations due to clinical and laboratory GI adverse experiences (AEs). General safety was also assessed, including adjudicated thrombotic cardiovascular event data. Efficacy was evaluated using the Patient Global Assessment of Disease Status (PGADS; 0-4 point scale). RESULTS: Mean (SD; maximum) duration of treatment was 19.3 (10.3; 32.9) and 19.1 (10.4; 33.1) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AEs was significantly lower with etoricoxib than diclofenac (5.2 vs 8.5 events per 100 patient-years, respectively; hazard ratio 0.62 (95% CI: 0.47, 0.81; p

The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept. METHODS: In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24. RESULTS: Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points. CONCLUSION: The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.

Reduction in the risk of developing back pain persists at least 30 months after discontinuation of teriparatide treatment: a meta-analysis.

INTRODUCTION: Teriparatide [rhPTH (1-34)] reduces fracture risk, and in a published meta-analysis of clinical trials, teriparatide-treated patients had reduced incidence of back pain relative to placebo or to antiresorptive drugs. The aim of this study was to evaluate back pain in teriparatide-treated versus comparator-treated patients during an interval including controlled clinical trials plus 30 months of additional follow-up. METHODS: A meta-analysis of four completed randomized, double-blinded trials of teriparatide [rhPTH (1-34)] versus comparator was performed. A multivariate Cox proportional hazards model was used to assess the heterogeneity of results and to estimate the relative risk of back pain. RESULTS: Patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.73 (95% CI, 0.61-0.87)], moderate or severe back pain [0.72 (0.58-0.89)], and severe back pain [0.39 (0.25-0.61)] compared with pooled controls, from initiation of the study drug through the end of follow-up. Sensitivity analysis showed that the results were robust to the removal of each individual trial from the meta-analysis. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results. CONCLUSIONS: Teriparatide-treated patients had a reduced incidence of back pain versus those receiving a comparator during an observation encompassing clinical trials plus 30 months of posttreatment observation.