Finding and keeping health care providers in rural communities: culture change in recruitment at rural health group.

Transforming rural primary care is possible only when leadership is committed to a core set of competencies. Northeastern North Carolina, not always seen as an attractive locale for health professionals, has been developing a primary care medical home that emphasizes team-based care built upon respect, trust, and professionalism.

Efficacy and safety of using auditory-motor entrainment to improve walking after stroke: a multi-site randomized controlled trial of InTandemTM.

Walking slowly after stroke reduces health and quality of life. This multi-site, prospective, interventional, 2-arm randomized controlled trial (NCT04121754) evaluated the safety and efficacy of an autonomous neurorehabilitation system (InTandemTM) designed to use auditory-motor entrainment to improve post-stroke walking. 87 individuals were randomized to 5-week walking interventions with InTandem or Active Control (i.e., walking without InTandem). The primary endpoints were change in walking speed, measured by the 10-meter walk test pre-vs-post each 5-week intervention, and safety, measured as the frequency of adverse events (AEs). Clinical responder rates were also compared. The trial met its primary endpoints. InTandem was associated with a 2x larger increase in speed (Δ: 0.14 ± 0.03 m/s versus Δ: 0.06 ± 0.02 m/s, F(1,49) = 6.58, p = 0.013), 3x more responders (40% versus 13%, χ2(1) ≥ 6.47, p = 0.01), and similar safety (both groups experienced the same number of AEs). The auditory-motor intervention autonomously delivered by InTandem is safe and effective in improving walking in the chronic phase of stroke.

Referring Attention-Deficit/Hyperactivity Disorder: Gaining Perspective From Advanced Practice Providers in Primary Care.

The objective of the current study is to identify provider, patient, and family characteristics associated with pediatric advanced practice provider (APP) decisions to refer to a subspecialist for diagnosis and management of attention-deficit/hyperactivity disorder (ADHD). We conducted a cross-sectional electronic survey of pediatric primary care APPs using member lists of professional organizations. T tests and chi-square analysis were conducted to identify group differences. Most respondents rated themselves as comfortable diagnosing and managing ADHD. We found no significant difference between groups based on comfort level or likelihood to refer. APPs working in suburban settings report significantly lower levels of comfort. Self-designation as the practice's primary provider for behavioral/mental health concerns had significantly higher levels of comfort and were less likely to refer. In a limited sample, most APPs reported comfort diagnosing and managing ADHD. Activities to identify and ameliorate gaps in ADHD knowledge and care need to consider this growing part of the workforce.

Impact of Flexible Circuit Bonding and System Integration on Energy Resolution of Cross-Strip CZT Detectors.

Cadmium zinc telluride (CZT) detectors enable high spatial resolution and high detection efficiency and are utilized for many gamma-ray and X-ray spectroscopy applications. In this article, we describe a stable bonding process and report on the characterization of cross-strip CZT detectors before and after bonding to flexible circuit. The bonding process utilizes gold stud bonding and polymer epoxy technique to bond the flexible circuits to two CZT crystals and form a detector module in an anode-cathode-cathode-anode (ACCA) configuration. The readout electronics is optimized in terms of shaper setting and steering electrode voltage. The average full-width half maximum (FWHM) energy resolution at 662 keV of 110 CZT crystals tested individually was 3.5% ± 0.59% and 4.75% ± 0.48% prebonded and post-bonded, respectively. No depth correction was performed in this study. The average FWHM energy resolution at 662 keV of the scaled-up system with 80 CZT crystals was 4.40% ± 0.53%, indicating the scaled-up readout electronics and stacking of the modules does not deteriorate performance. The proper shielding and grounding of the scaled-up system slightly improved the system-wide performance. The FWHM energy resolution at 511 keV of the scaled-up system was 5.85% ± 0.73%.

Autonomous Control of Music to Retrain Walking After Stroke.

BACKGROUND: Post-stroke care guidelines highlight continued rehabilitation as essential; however, many stroke survivors cannot participate in outpatient rehabilitation. Technological advances in wearable sensing, treatment algorithms, and care delivery interfaces have created new opportunities for high-efficacy rehabilitation interventions to be delivered autonomously in any setting (ie, clinic, community, or home). METHODS: We developed an autonomous rehabilitation system that combines the closed-loop control of music with real-time gait analysis to fully automate patient-tailored walking rehabilitation. Specifically, the mechanism-of-action of auditory-motor entrainment is applied to induce targeted changes in the post-stroke gait pattern by way of targeted changes in music. Using speed-controlled biomechanical and physiological assessments, we evaluate in 10 individuals with chronic post-stroke hemiparesis the effects of a fully-automated gait training session on gait asymmetry and the energetic cost of walking. RESULTS: Post-treatment reductions in step time (Δ: -12 ± 26%, P = .027), stance time (Δ: -22 ± 10%, P = .004), and swing time (Δ: -15 ± 10%, P = .006) asymmetries were observed together with a 9 ± 5% reduction (P = .027) in the energetic cost of walking. Changes in the energetic cost of walking were highly dependent on the degree of baseline energetic impairment (r =- .90, P < .001). Among the 7 individuals with a baseline energetic cost of walking larger than the normative value of healthy older adults, a 13 ± 4% reduction was observed after training. CONCLUSIONS: The closed-loop control of music can fully automate walking rehabilitation that markedly improves walking after stroke. Autonomous rehabilitation delivery systems that can safely provide high-efficacy rehabilitation in any setting have the potential to alleviate access-related care gaps and improve long-term outcomes after stroke.

Feasibility and Proof-of-Concept of Delivering an Autonomous Music-Based Digital Walking Intervention to Persons with Parkinson's Disease in a Naturalistic Setting.

BACKGROUND: Reduced motor automaticity in Parkinson's disease (PD) negatively impacts the quality, intensity, and amount of daily walking. Rhythmic auditory stimulation (RAS), a clinical intervention shown to improve walking outcomes, has been limited by barriers associated with the need for ongoing clinician input. OBJECTIVE: To assess the feasibility, proof-of-concept, and preliminary clinical outcomes associated with delivering an autonomous music-based digital walking intervention based on RAS principles to persons with PD in a naturalistic setting. METHODS: Twenty-three persons with PD used the digital intervention independently for four weeks to complete five weekly 30-minute sessions of unsupervised, overground walking with music-based cues. The intervention progressed autonomously according to real-time gait sensing. Feasibility of independent use was assessed by examining participant adherence, safety, and experience. Intervention proof-of-concept was assessed by examining spatiotemporal metrics of gait quality, daily minutes of moderate intensity walking, and daily steps. Preliminary clinical outcomes were assessed following intervention completion. RESULTS: Participants completed 86.4% of sessions and 131.1% of the prescribed session duration. No adverse events were reported. Gait speed, stride length, and cadence increased within sessions, and gait variability decreased (p < 0.05). Compared to baseline, increased daily moderate intensity walking (mean Δ= +21.44 minutes) and steps (mean Δ= +3,484 steps) occurred on designated intervention days (p < 0.05). Quality of life, disease severity, walking endurance, and functional mobility were improved after four weeks (p < 0.05). CONCLUSIONS: Study findings supported the feasibility and potential clinical utility of delivering an autonomous digital walking intervention to persons with PD in a naturalistic setting.

Perceived social support from strength and conditioning coaches among injured student athletes.

Injuries suffered by student athletes not only affect their physical ability to perform in sport but also have psychological effects as well. The purpose of this study was to examine student athletes' perceptions, expectations, and satisfaction of the social support provided by their strength and conditioning coach (SC) during the later reconditioning stage of their rehabilitation and their views on the overall level of importance of each type of social support. One hundred and sixty-five participants aged 20.21 ± 1.32 years from 6 Division I Universities in the Midwest region of the USA completed the modified Social Support Survey. The results of a chi-square test assessing the responses for 6 types of social support provided by SCs based on athletes' age, gender, and sport revealed a significant difference (χ2[13,105] = 26.46, p = 0.015) for listening support differing by sport. A significant difference (χ2[13,105] = 267.74, p = 0.010) was also revealed for reported emotional challenge by sport. Results showed that the SC had a significant psychosocial impact on student-athletes' overall psychological well-being during reconditioning. This study provides evidence of the vital psychosocial role that SCs can play during an injured student-athlete's reconditioning program.

A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease.

Children with hemodynamically significant congenital heart disease (CHD) are at risk for serious respiratory syncytial virus (RSV) disease. This study was designed to assess the safety and tolerability of motavizumab versus palivizumab in children with CHD and was not powered for efficacy. Patients (n = 1236) aged ≤24 mo were randomized to receive five monthly doses (15 mg/kg) of motavizumab or palivizumab during the RSV season. Adverse events (AEs) and serious AEs (SAEs) were recorded through 30 d after the last dose. RSV hospitalizations and RSV outpatient medically attended lower respiratory tract infections (MALRI; season 2) were summarized. Approximately 93 and 50% of patients reported an AE or SAE, respectively. Skin events occurred in 19.3% of motavizumab recipients and 16.2% of palivizumab recipients. Rates of hospitalizations and RSV MALRI were similar between treatment groups [relative risk (RR): 0.75; 95% CI, 0.34-1.59 and RR: 0.49; 95% CI, 0.10-1.99, respectively; both p > 0.05]. Motavizumab and palivizumab had similar safety profiles in children with hemodynamically significantly CHD; with the exception of skin events which were increased in motavizumab recipients. Safety and efficacy were consistent with another study comparing motavizumab with palivizumab in premature infants without CHD.

Cost of community integrated prevention campaign for malaria, HIV, and diarrhea in rural Kenya.

BACKGROUND: Delivery of community-based prevention services for HIV, malaria, and diarrhea is a major priority and challenge in rural Africa. Integrated delivery campaigns may offer a mechanism to achieve high coverage and efficiency. METHODS: We quantified the resources and costs to implement a large-scale integrated prevention campaign in Lurambi Division, Western Province, Kenya that reached 47,133 individuals (and 83% of eligible adults) in 7 days. The campaign provided HIV testing, condoms, and prevention education materials; a long-lasting insecticide-treated bed net; and a water filter. Data were obtained primarily from logistical and expenditure data maintained by implementing partners. We estimated the projected cost of a Scaled-Up Replication (SUR), assuming reliance on local managers, potential efficiencies of scale, and other adjustments. RESULTS: The cost per person served was $41.66 for the initial campaign and was projected at $31.98 for the SUR. The SUR cost included 67% for commodities (mainly water filters and bed nets) and 20% for personnel. The SUR projected unit cost per person served, by disease, was $6.27 for malaria (nets and training), $15.80 for diarrhea (filters and training), and $9.91 for HIV (test kits, counseling, condoms, and CD4 testing at each site). CONCLUSIONS: A large-scale, rapidly implemented, integrated health campaign provided services to 80% of a rural Kenyan population with relatively low cost. Scaling up this design may provide similar services to larger populations at lower cost per person.

Establishment of soil strength in a nourished wetland using thin layer placement of dredged sediment.

Coastal wetlands are experiencing accelerated rates of fragmentation and degradation due to sea-level rise, sediment deficits, subsidence, and salt-water intrusion. This reduces their ability to provide ecosystem benefits, such as wave attenuation, habitat for migratory birds, and a sink for carbon and nitrogen cycles. A deteriorated back barrier wetland in New Jersey, USA was nourished through thin layer placement (TLP) of dredged sediment in 2016. A field investigation was conducted in 2019 using a cone penetrometer (CPT) to quantify the establishment of soil strength post sediment nourishment compared to adjacent reference sites in conjunction with traditional wetland performance measures. Results show that the nourished area exhibited weaker strengths than the reference sites, suggesting the root system of the vegetation is still establishing. The belowground biomass measurements correlated to the CPT strength measurements, demonstrating that shear strength measured from the cone penetrometer could serve as a surrogate to monitor wetland vegetation trajectories. In addition, heavily trafficked areas underwent compaction from heavy equipment loads, inhibiting the development of vegetation and highlighting how sensitive wetlands are to anthropogenic disturbances. As the need for more expansive wetland restoration projects grow, the CPT can provide rapid high-resolution measurements across large areas supplying government and management agencies with vital establishment trajectories.

Spiritual well-being in long-term survivors with chronic graft-versus-host disease after hematopoietic stem cell transplantation.

Spiritual well-being (Sp-WB) is a resource that supports adaptation and resilience, strengthening quality of life (QOL) in patients with cancer or other chronic illnesses. However, the relationship between Sp-WB and QOL in patients with chronic graft-versus-host disease (cGVHD) remains unexamined. Fifty-two participants completed the Functional Assessment of Chronic Illness Therapy-Spiritual WellBeing (FACIT-Sp) questionnaire as part of a multidisciplinary study of cGVHD. Sp-WB was generally high. Those with the lowest Sp-WB had a significantly longer time since diagnosis of cGVHD (P = 0.05) than those with higher Sp-WB. There were no associations between Sp-WB and demographics, cGVHD severity, or intensity of immunosuppression. Participants with the lowest Sp-WB reported inferior physical (P = 0.0009), emotional (P = 0.003), social (P = 0.027), and functional well-being (P < 0.0001) as well as lower overall QOL (P < 0.0001) compared with those with higher Sp-WB. They also had inferior QOL relative to population norms. Differences between the group reporting the lowest Sp-WB and those groups who reported the highest Sp-WB scores consistently demonstrated a significant difference for all QOL subscales and for overall QOL. Controlling for physical, emotional, and social well-being, Sp-WB was a significant independent predictor of contentment with QOL. Our results suggest that Sp-WB is an important factor contributing to the QOL of patients with cGVHD. Research is needed to identify factors that diminish Sp-WB and to test interventions designed to strengthen this coping resource in patients experiencing the late effects of treatment.

A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season.

BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide. High-risk infants currently receive RSV prophylaxis with palivizumab, a humanized RSV monoclonal antibody (MAb). In preclinical in vitro and in vivo (cotton-rat model) studies, motavizumab, a new RSV MAb, was shown to have greater anti-RSV activity than palivizumab. Motavizumab is currently under review for licensing approval. Since both MAbs may be available concurrently, this study evaluated their safety and tolerability when administered sequentially during the same RSV season. METHODS: Between April 2006 and May 2006, 260 high-risk infants were randomly assigned 1:1:1 to receive monthly intramuscular injections: 2 doses of motavizumab followed by 3 doses of palivizumab (M/P); 2 doses of palivizumab followed by 3 doses of motavizumab (P/M); or 5 doses of motavizumab (control). Adverse events (AEs, serious AEs [SAEs]), development of antidrug antibody (ADA), and serum drug trough concentrations were assessed. RESULTS: Most children received all 5 doses (246/260 [94.6%]) and completed the study (241/260 [92.7%]). While overall AE rates were similar (mostly level 1 or 2 in severity), SAEs and level 3 AEs occurred more frequently in the M/P group (SAEs: 22.9% M/P, 8.4% P/M, 11.8% motavizumab only; level 3 AEs: 15.7% M/P, 6.0% P/M, 6.5% motavizumab only). This trend in AE rates occurred before and after switching from motavizumab to palivizumab, suggesting a cause other than the combined regimen. Frequencies of AEs judged by the investigator to be related to study drug were similar among groups. Two deaths occurred on study (both in the M/P group, before palivizumab administration); neither was considered by the site investigator to be related to study drug. Mean serum drug trough concentrations were comparable among groups; ADA detection was infrequent (5.1% or less of any group). CONCLUSIONS: The conclusions drawn from this study are limited by the small sample size per group. However, within this small study, overall AE rates, serum drug trough concentrations, and development of ADA associated with administering motavizumab and palivizumab sequentially to high-risk children appear comparable to administering motavizumab alone during the same RSV season. TRIAL REGISTRATION: clinicaltrials.gov NCT00316264.

A Music-Based Digital Therapeutic: Proof-of-Concept Automation of a Progressive and Individualized Rhythm-Based Walking Training Program After Stroke.

BACKGROUND: The rhythm of music can entrain neurons in motor cortex by way of direct connections between auditory and motor brain regions. OBJECTIVE: We sought to automate an individualized and progressive music-based, walking rehabilitation program using real-time sensor data in combination with decision algorithms. METHODS: A music-based digital therapeutic was developed to maintain high sound quality while modulating, in real-time, the tempo (ie, beats per minute, or bpm) of music based on a user's ability to entrain to the tempo and progress to faster walking cadences in-sync with the progression of the tempo. Eleven individuals with chronic hemiparesis completed one automated 30-minute training visit. Seven returned for 2 additional visits. Safety, feasibility, and rehabilitative potential (ie, changes in walking speed relative to clinically meaningful change scores) were evaluated. RESULTS: A single, fully automated training visit resulted in increased usual (∆ 0.085 ± 0.027 m/s, P = .011) and fast (∆ 0.093 ± 0.032 m/s, P = .016) walking speeds. The 7 participants who completed additional training visits increased their usual walking speed by 0.12 ± 0.03 m/s after only 3 days of training. Changes in walking speed were highly related to changes in walking cadence (R2 > 0.70). No trips or falls were noted during training, all users reported that the device helped them walk faster, and 70% indicated that they would use it most or all of the time at home. CONCLUSIONS: In this proof-of-concept study, we show that a sensor-automated, progressive, and individualized rhythmic locomotor training program can be implemented safely and effectively to train walking speed after stroke. Music-based digital therapeutics have the potential to facilitate salient, community-based rehabilitation.

Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children.

BACKGROUND: : Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children. Motavizumab is an investigational humanized monoclonal antibody for RSV prophylaxis. METHODS: : A dose-escalation study was conducted followed by assessment of safety, tolerability, serum concentrations, and immunogenicity during a second consecutive RSV season. In season 1, premature infants aged < or =6 months or children < or =24 months with chronic lung disease of prematurity received monthly motavizumab (3 or 15 mg/kg). In season 2, children who received > or =3 motavizumab doses in season 1 were randomized to receive monthly motavizumab or palivizumab 15 mg/kg. RESULTS: : Of 217 children enrolled in season 1, 211 (97.2%) received motavizumab 15 mg/kg and 205 (94.5%) patients completed the study through 90 days after the final dose. In season 2, 136 children were randomized to receive motavizumab (n = 66) or palivizumab (n = 70). The most commonly reported related adverse event was transient injection site erythema. In season 1, mean trough motavizumab concentrations were 7.9 and 50.2 microg/mL after the 3- and 15-mg/kg doses, respectively. Trough concentrations increased with repeated motavizumab dosing; a similar pattern was seen in season 2. Antimotavizumab reactivity occurred infrequently (3.3%) in season 1. In season 2, no treatment group-specific antidrug antibody was detected through 90 to 120 days after dosing with either product. CONCLUSIONS: : The pharmacokinetic profile of motavizumab was similar to that of other IgG1 antibodies. Increased adverse reactions or immunogenicity were not observed during and after a second season of treatment with motavizumab. Safety findings from these studies supported the continued development of motavizumab.

Wetland Shear Strength with Emphasis on the Impact of Nutrients, Sediments, and Sea Level Rise.

This paper presents a comprehensive review of shear strength measurements in wetland soils, which can be used to make inferences of the influence of nutrients and sediments on wetland health. Ecosystem restoration is increasing across the Gulf of Mexico and in other coastal systems, with management questions related to soil strength among the most critical to address for the sustainability of restoration programs. An overview of geotechnical engineering principles is provided as a starting point to understand basic soil mechanics concepts of stress, effective stress, pore-water pressure, unit weight, and shear strength. The review of wetland shear strength measurements focuses on the hand-held vane shear, torvane, cone penetrometer, and wetland soil strength tester. This synthesis shows that vane shear measurements can identify the shear strength trend in horizontal and vertical spaces and may be an indicator of wetland soil strength. However, the significant uncertainty of the vane shear measurements may preclude making conclusions about shear strength values without further testing and calibration of the devices. The torvane results show considerable scatter such that it is not recommended for quantitative shear strength measurements. The cone penetrometer represents a technique that is independent of operators and provides a high density of measurements with depth. It signifies the state-of-practice of wetland shear strength testing and is a reasonable tool to measure spatial and temporal variations in soil strength and other geotechnical properties (e.g., pore-water pressure, soil moisture, resistivity, and temperature) in wetlands. The wetland soil strength tester provides insight into the wetland soil resistance in the first 15 cm, which is the zone where most belowground biomass is present. Recommended future research includes evaluating the uncertainty in all in-situ soil strength testing methods, developing relationships between different field instruments, and establishing consistent statistical methods and field-testing procedures to make inferences and assessments.

Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction.

Current clinically-tested nicotine vaccines have yet shown enhanced smoking cessation efficacy due to their low immunogenicity. Achieving a sufficiently high immunogenicity is a necessity for establishing a clinically-viable nicotine vaccine. This study aims to facilitate the immunogenicity of a hybrid nanoparticle-based nicotine vaccine by rationally incorporating toll-like receptor (TLR)-based adjuvants, including monophosphoryl lipid A (MPLA), Resiquimod (R848), CpG oligodeoxynucleotide 1826 (CpG ODN 1826), and their combinations. The nanoparticle-delivered model adjuvant was found to be taken up more efficiently by dendritic cells than the free counterpart. Nanovaccine particles were transported to endosomal compartments upon cellular internalization. The incorporation of single or dual TLR adjuvants not only considerably increased total anti-nicotine IgG titers but also significantly affected IgG subtype distribution in mice. Particularly, the nanovaccines carrying MPLA+R848 or MPLA+ODN 1826 generated a much higher anti-nicotine antibody titer than those carrying none or one adjuvant. Meanwhile, the anti-nicotine antibody elicited by the nanovaccine adjuvanted with MPLA+R848 had a significantly higher affinity than that elicited by the nanovaccine carrying MPLA+ODN 1826. Moreover, the incorporation of all the selected TLR adjuvants (except MPLA) reduced the brain nicotine levels in mice after nicotine challenge. Particularly, the nanovaccine with MPLA+R848 exhibited the best ability to reduce the level of nicotine entering the brain. Collectively, rational incorporation of TLR adjuvants could enhance the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine, making it a promising next-generation immunotherapeutic candidate for treating nicotine addiction.

Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: a phase 3 randomised double-blind placebo-controlled trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections. METHODS: This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation. Participants were randomly assigned (2:1) to receive either five monthly intramuscular doses of motavizumab (15 mg/kg) or placebo. They were followed up for 150 days after the first dose, and the primary endpoints were respiratory admission to hospital with a positive result for RSV by RT-PCR and death caused by RSV. Participants were followed up for medically attended wheezing until they reached age 3 years. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00121108. FINDINGS: During the autumn seasons (October to December) between 2004 and 2007, 2127 infants of the 2596 infants enrolled were randomly assigned to receive either motavizumab (1417) or placebo (710). After ITT analysis, motavizumab resulted in an 87% relative reduction (relative risk [RR] 0·13, 95% CI 0·08-0·21) in the proportion of infants admitted to hospital with RSV (21 [2%] of 1417 participants who received motavizumab; 80 [11%] of 710 participants who received placebo, p<0·0001). Serious adverse events were less common in particpants taking motavizumab (212 [15%]) than particpants on placebo (148 [21%]). Six deaths occurred in study participants (motavizumab, n=4 [0·3%]; placebo, n=2 [0·3%]); none were deemed to be related to the study product. Hypersensitivity events were more common in patients given motavizumab (208 [14·7%]) than in placebo recipients (87 [12·3%]; p=0·14). There was no effect on rates of medically attended wheezing in children aged 1-3 years (190 [14·9%] of participants randomly assigned to receive motavizumab vs 90 [14·0%] participants randomly assigned to receive placebo). INTERPRETATION: To our knowledge, this is the only trial of an anti-RSV antibody to prevent serious RSV disease in healthy term infants. Motavizumab significantly reduced the RSV-associated inpatient and outpatient burden and set a benchmark for the efficacy of RSV prevention strategies. The findings do not support a direct, generalisable, causal association between RSV lower respiratory tract infection and subsequent long-term wheezing in term infants. FUNDING: MedImmune.

Is there an association between life events, postnatal depression and thyroid dysfunction in thyroid antibody positive women?

BACKGROUND: Postnatal depression is more common in women positive for thyroid autoantibodies, independent of thyroid hormone dysfunction, but the basis of this association is unclear. AIMS: The objective of the work reported here has been to investigate from data obtained from previously published research, a possible association between life events, postnatal depression and the development of thyroid dysfunction in women who are positive for thyroid autoantibodies. METHOD: A cohort of pregnant women whose thyroid antibody status was positive (N = 115), was identified at antenatal booking (approximately 16 weeks). These, and a group of women negative for thyroid antibodies (N = 123), were assessed for depression at six to eight weeks postpartum and then at 12, 20 and 28 weeks postpartum according to Research Diagnostic Criteria (RDC). The number and type of life events over the preceding year were also assessed at eight weeks postpartum using Paykel's Life Event Schedule. At four weekly intervals post-partum until six months, thyroid antibody levels and thyroid function (plasma T3 T4 and TSH) were measured. RESULTS: As anticipated, the thyroid antibody status remained the same throughout the study, and there was no difference in the number or type of life events reported in the preceding year, between antibody positive and antibody negative women. Postnatal depression was associated with an excess of both total and negative life events, independent of thyroid antibody status or actual thyroid hormonal status. Women who developed thyroid dysfunction did not report an excess of life events (total, negative or neutral) in the preceding year. CONCLUSION: There was an excess of reported total and negative life events in women with postnatal depression, but this was independent of thyroid antibody status or function.

Randomized, Double-Blind Study of the Safety of the Liquid Versus Lyophilized Formulation of Palivizumab in Premature Infants and Children with Chronic Lung Disease of Prematurity.

INTRODUCTION: To avoid the need for reconstitution required by lyophilized palivizumab, a liquid formulation was developed. This study assessed the safety and antidrug antibodies (ADA) of the liquid formulation of palivizumab compared with the lyophilized formulation. METHODS: This phase 4, randomized, double-blind, multicenter study included children with chronic lung disease of prematurity who were ≤24 months of age and children born prematurely with a gestational age of ≤35 weeks who were ≤6 months of age at randomization. Subjects were randomized 1:1 to 15 mg/kg of either liquid or lyophilized palivizumab administered via intramuscular injection every 30 days for a total of 5 injections. Safety was assessed based on serious adverse events (SAEs). ADA to palivizumab was assessed using blood collected at baseline and at a time point between study days 240 and 300. RESULTS: A total of 413 subjects were included in the analyses. The incidence of SAEs reported was 8.5% with liquid palivizumab and 5.9% with lyophilized palivizumab; none were deemed drug-related. The reported SAEs were consistent with expected conditions in this pediatric age group; there was no increase in respiratory syncytial virus (RSV) disease with liquid palivizumab. At study days 240-300, antipalivizumab antibodies were detected in none of the subjects in the liquid palivizumab group and in 1 subject in the lyophilized group. The true ADA percent positive, based on the upper limit of the 95% confidence interval (CI), was <1.5% for both treatments combined. CONCLUSION: The frequency of detection of ADAs was low. The true ADA percent positive for both treatment groups combined based on the upper limit of the 95% CI was <1.5%. The type and frequency of SAEs reported were as expected, and there was no evidence of an increase in RSV disease with liquid palivizumab.