Implementing integrated care guidelines in asthma and COPD: It ain't easy!

Objective: To evaluate the implementation of a guideline-based, integrated, standardised, personal approach in patients with Chronic Obstructive Pulmonary Disease (COPD) or Asthma in a real-life situation. Methods: Patients at the outpatient clinic of the department of pulmonary disease were included in a controlled cohort study, comparing the use of diagnostic items and 'Personalised care plans' (PCPs) in patients with obstructive lung disease before (2013) and after (2015) implementation of a personalised diagnostic pathway. Results were compared with reference data (2016) from two control hospitals that used the same guidelines but did not implement this pathway. Results: 100 patients were selected for all three cohorts. After implementing the diagnostic pathway in 2015, 35 % of patients visited attended all pre-planned appointments, whereas 65 % of patients did not: they were diagnosed using usual care. Factors contributing to patients not attending the diagnostic care pathway were: the logistical complexity and intensity of the 2-day pathway, patients willingness to participate in a personalised pathway, and low social economic status or low literacy. After the implementation of the pathway, a significant improvement was seen in the number of PCPs (P < 0.001) and the number of diagnostic items registered recorded in the patients' electronic medical records (P < 0.001). Conclusion: Implementing a standardised diagnostic pathway in a real-life population significantly improved the number of personalised care plans, demonstrating that the implementation of holistic care planning is feasible in this population. Nevertheless, the pathway needs further improvements to maximize the number of patients benefitting from it, including logistical streamlining, removing unnecessary diagnostic tools, and increasing the focus on low literacy. Additionally, we found that implementing existing guidelines in a real life context is complex. Therefore, it is required to prioritize the translation of current guidelines into every-day practice, before expanding existing guidelines and protocols.

Ecogenomics and metabolic potential of the South Atlantic Ocean microbiome.

The unique combination of depth, salinity, and water masses make the South Atlantic Ocean an ecosystem of special relevance within the global ocean. Yet, the microbiome of this ecosystem has received less attention than other regions of the global Ocean. This has hampered our understanding of the diversity and metabolic potential of the microorganisms that dwell in this habitat. To fill this knowledge gap, we analyzed a collection of 31 metagenomes from the Atlantic Ocean that spanned the epipelagic, mesopelagic and bathypelagic zones (surface to 4000 m). Read-centric and gene-centric analysis revealed the unique taxonomic and functional composition of metagenomes from each depth zone, which was driven by differences in physical and chemical parameters. In parallel, a total of 40 metagenome-assembled genomes were obtained, which recovered one third of the total community. Phylogenomic reconstruction revealed that many of these genomes are derived from poorly characterized taxa of Bacteria and Archaea. Genomes derived from heterotrophic bacteria of the aphotic zone displayed a large apparatus of genes suited for the utilization of recalcitrant organic compounds such as cellulose, chitin and alkanes. In addition, we found genomic evidence suggesting that mixotrophic bacteria from the bathypelagic zone could perform carbon fixation through the Calvin-Benson-Bassham cycle, fueled by sulfur oxidation. Finally, we found that the viral communities shifted throughout the water column regarding their targeted hosts and virus-to-microbe ratio, in response to shifts in the composition and functioning their microbial counterparts. Our findings shed light on the microbial and viral drivers of important biogeochemical processes that take place in the South Atlantic Ocean.

Neutron-diffraction study of structural transition and magnetic order in orthorhombic and rhombohedral La(7/8)Sr(1/8)Mn(1-γ)O(3+δ).

We report on a systematic neutron powder diffraction (NPD) study of polycrystalline La(7/8)Sr(1/8)Mn(1-γ)O(3+δ) compounds. We investigated the structural and magnetic phases and transitions in the temperature range between 10 and 900 K for two different samples: an Ar-annealed sample with an orthorhombic Pbnm (Z = 4; O) structure at room temperature and an air-sintered sample with a rhombohedral [Formula: see text] (Z = 2;R) structure at room temperature. At higher temperatures, above 400 K, both samples exhibit a rhombohedral structure. For the Ar-annealed sample, a Jahn-Teller (JT) transition occurs in the orthorhombic phase at about 298 K with very large variations in the Mn-O2' and Mn-O2 bond lengths and Mn-O1-Mn bond angle on cooling from 298 to 180 K. For this sample the ferromagnetic moment at 10 K in the magnetic space group Pb'n'm amounts to 3.22(5) µ(B)/Mn. In contrast, the air-sintered sample undergoes on cooling a structural transition from rhombohedral (R) to orthorhombic (O) with a mixed phase of nearly equal R and O repartition at 120 K. Ferromagnetic order develops in this sample at about 240 K with a low-temperature moment of 3.35(4) µ(B)/Mn at 10 K. The coherent JT distortion in its orthorhombic phase occurs below some 170 K. In addition, we have determined the coherent JT distortion parameter Δ, the tolerance factor t and the one-electron bandwidth W of the e(g)-band.

Recrecimiento óseo después de la cirugía descompresiva por estenosis del canal lumbar / Bone regrowth after surgical decompression for lumbar spinal stenosis

Objetivo: Determinar la incidencia y el grado de recrecimiento óseo que ocurre en el sitio de la laminectomía después de efectuar cirugía descompresiva para la estenosis del canal lumbar e investigar la existencia de posibles factores que pueden promover dicho recrecimiento y sus posible influencia en la evolución clínica. Material y método: Se revisaron 29 pacientes operados por estenosis lumbar, con un seguimiento de 6,6 años. Se compararon las imágenes radiográficas del arco posterior del postoperatorio inmediato con las obtenidas en el último control. El recrecimiento se evaluó como un porcentaje del hueso recrecido con el defecto de la laminectomía original. Se establecieron 4 grados: Insignificante 0-10%, leve 11-40%, moderado 41-70%, grave 71-100%. Se analizaron los aspectos relacionados con el sexo, etiología de la estenosis, número de niveles, tipo de cirugía, grado de recrecimiento y clínica del último control. Resultados. En 9 casos no se observó recrecimiento o era insignificante, en 18 se calificó como leve y en 2 como moderado. No se encontró ningún caso grave. El grado de recrecimiento estaba relacionado con el número de niveles intervenidos y con la práctica o no de artrodesis. El grado de recrecimiento leve y moderado ha tenido peores resultados que el grupo de recrecimiento insignificante. Conclusión: el recrecimiento óseo parece ser un factor de deterioro de la clínica, aunque el resultado de nuestro estudio no es estadísticamente significativo

Objective: To determine the incidence and the amount of bony regrowth occurring at the site of laminectomy after performing decompressive surgery for lumbar spinal stenosis and to investigate the existence of possible factors that could enhance such bony regrowth and its possible influence in clinical outcome. Methods: Bone regrowth was assessed in 29 patients (mean follow-up 6,6 years) that underwent decompressive surgery due to lumbar spinal canal stenosis. Postoperative plain films were compared with plain films obtained at the last follow-up. Bone regrowth was graded relating to the percentage of new bone created at the site of the laminectomy being divided into four categories: insignificant 0-10%, mild 11-40%, moderate 41-70% and severe 71-100%. Different factors such as gender, spinal stenosis etiology, number of levels involved in surgery, degree of bony regrowth and patient clinical condition at the last follow-up were analyzed. Results: In 9 patients none or insignificant bony regrowth was observed, 18 patients were included in the mild category whereas 2 patients were included in the moderate category. No case of severe regrowth was identified. The degree of bony regrowth was found to be related with the number of levels included in the surgery and with the performance or not of spinal arthrodesis. Regarding clinical outcome those patients showing mild to moderate bone regrowth showed a worse clinical outcome than those who presented insignificant amounts of bony regrowth. Conclusions: Although the results of the present study are not statistically significant it seems that the occurrence of bony regrowth at the site of laminectomy might be a deleterious factor for clinical outcome in those patients who underwent decompressive surgery for lumbar spinal stenosis

Genetic susceptibility to keloid disease: mutation screening of the TGFbeta3 gene.

Keloid disease (KD) is a fibroproliferative dermal tumour of unknown aetiology. The increased familial clustering in KD, its increased prevalence in certain races and its presence in identical twins suggest a strong genetic predisposition to keloid formation. Transforming growth factor beta isoforms (TGFbeta) play a central role in wound healing and fibrosis and have been implicated in KD pathogenesis. Recent data has suggested that TGFbeta(3) has an important role in scar formation. There is little known about the genetic variation present within the TGFbeta(3) gene, which contains seven exons and six introns spanning 43,000 base pairs of the human genome. Exons one to seven and the promoter region (1000 bp upstream from exon 1 in the 5'-flanking regions) were screened in 95 Caucasian KD cases and 95 Caucasian controls for the presence of novel mutations using a high throughput DHPLC mutation detection technology. There were no mutations identified in any of the exonic regions, however, multiple nondisease associated mutations were found in the promoter region of the TGFbeta(3) gene. These data demonstrate that there is no association between the exonic and promoter regions of TGFbeta(3) gene and keloid scarring in our cohort of Caucasian patients.

Rapid denaturing high-performance liquid chromatography (DHPLC) for mutation scanning of the transforming growth factor beta3 gene using a novel proof-reading polymerase.

We have utilized a novel variation on the conventional denaturing high-performance liquid chromatography (DHPLC) technology, which we term rapid DHPLC, combining changes in instrumentation, cartridge technology and analysis conditions to enable significant increases in throughput to be achieved. In addition, the use of a novel proof-reading polymerase for sample amplification with a low misincorporation rate enables simplification of the DHPLC patterns and hence enhanced mutation detection recognition. This scheme for increasing DHPLC throughput has been tested by scanning the transforming growth factor (TGF) beta3 gene for the presence of mutations for which there is limited published or on-line data available regarding the presence of gene polymorphisms. TGFbeta isoforms have multiple roles in cell division, growth, proliferation, transformation and differentiation. TGFbeta3 is a TGFbeta cytokine isoform, and has an important role in embryogenesis, cell differentiation and wound healing. The TGFbeta3 gene consists of seven exons and six introns spanning 43 000 bp of the human genome on chromosome 14q23-24. The rapid DHPLC approach enabled scanning of all seven exons and part of the promoter region (1000 bp upstream from exon 1 in the 5'-flanking regions) of the TGFbeta3 gene in 95 Caucasian individuals in only 8 days, in comparison to the 17 days it would have previously taken. Mutations were clearly identified in the promoter region of the TGFbeta3 gene but were absent from the exonic regions. Understanding the genetic variations affecting the TGFbeta3 gene is important as this molecule has multiple regulatory functions on a variety of cell types.

Double-blind, placebo-controlled study of single-dose amphetamine formulations in ADHD.

OBJECTIVE: To compare the efficacy and time course of single morning doses of Adderall, extended-release, and immediate-release dextroamphetamine sulfate. METHOD: Thirty-five children with attention-deficit/hyperactivity disorder, combined type, were given Adderall, immediate-release dextroamphetamine, dextroamphetamine Spansules, and placebo in a randomized, double-blind, crossover study. Behavior ratings, locomotor activity measurements, and academic measures were obtained over a period of 8 weeks. RESULTS: All three drugs exhibited robust efficacy versus placebo on nearly all measures. The effects of dextroamphetamine Spansules were less robust in the morning, particularly compared with Adderall, but they lasted 3 to 6 hours longer, depending on the measure. Although parent behavior ratings and locomotor activity showed improvements up to 12 hours after single doses of all three drugs, the number of math problems attempted and completed correctly 4 hours after dosing were only robustly increased by Spansules. CONCLUSIONS: Both immediate-release amphetamines demonstrated earlier onset of effects, but dextroamphetamine Spansules showed more sustained effects that were present on a wider range of measures.

[Comparison of optical methods for estimating the opening of the canopy and leaf area in leafy forests]. / Comparaison de méthodes optiques pour estimer l'ouverture de la canopée et l'indice foliaire en forêt feuillue.

Based on inversion of gap fraction data (Poisson model of foliage distribution), three optical methods using the Demon, the Plant Canopy Analyzer LAI-2000 (PCA) and hemispherical photographs, have been compared to estimate canopy openness (CO) and leaf area index (LAI) in a mature, neutrophil, oak-beech-hornbeam forest on mull in eastern France. Mean CO over the whole hemisphere was similar for PCA (7.9%) and hemispherical photographs (8.0%). The needle method, a vertical point quadrat method, applied to the litter after leaf fall has served as a reference to LAI (4.7). The Demon provided the estimate (4.9) closest to the reference value. The PCA and hemispherical photographs underestimate mean LAI by 30% (3.3) and 19% (3.8), respectively, if used without correction. Based on fish-eye sensors, LAI estimates can be improved if 3 annuli (4.2) or 2 annuli (4.5) are used in place of 5 with the PCA, or by means of logarithmic averaging of gap fractions over azimuth at an appropriate angular resolution (180 degrees: 4.6, or 120 degrees: 5.2) with hemispherical photographs. Not taking into account azimuthal variation in gap fraction distribution generates a more important error than the error induced by light scattering near horizon. In order to improve LAI estimates, an original iterative procedure is presented, which allows the simultaneous calculation of LAI over a broad range of angular azimuthal resolutions.

Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic studies of boys with attention-deficit/hyperactivity disorder (ADHD) have detected decreased volumes in total and frontal brain, basal ganglia, and cerebellar vermis. We tested these findings in a sample of girls with ADHD. METHODS: Anatomic brain magnetic resonance images from 50 girls with ADHD, of severity comparable with that in previously studied boys, and 50 healthy female control subjects, aged 5 to 15 years, were obtained with a 1.5-T scanner with contiguous 2-mm coronal slices and 1.5-mm axial slices. We measured volumes of total cerebrum, frontal lobes, caudate nucleus, globus pallidus, cerebellum, and cerebellar vermis. Behavioral measures included structured psychiatric interviews, parent and teacher ratings, and the Wechsler vocabulary and block design subtests. RESULTS: Total brain volume was smaller in girls with ADHD than in control subjects (effect size, 0.40; P =.05). As in our previous study in boys with ADHD, girls with ADHD had significantly smaller volumes in the posterior-inferior cerebellar vermis (lobules VIII-X; effect size, 0.54; P =.04), even when adjusted for total cerebral volume and vocabulary score. Patients and controls did not differ in asymmetry in any region. Morphometric differences correlated significantly with several ratings of ADHD severity and were not predicted by past or present stimulant drug exposure. CONCLUSIONS: These results confirm previous findings for boys in the posterior-inferior lobules of the cerebellar vermis. The influence of the cerebellar vermis on prefrontal and striatal circuitry should be explored.

The computation of forest leaf area index on slope using fish-eye sensors.

Leaf area index (LAI) measured with fish-eye sensors is inevitably affected by slope. In order to quantify this effect, LAIs measured in contrasted forests were corrected for slope. Digitised hemispherical photographs were analysed to compute LAI according to azimuth and as a function of slope. The topographic mask (part of hemisphere obstructed by slope) and the path length of a ray of light at a given zenith angle (longer upslope and shorter downslope) were taken into account. Results indicate a strong slope effect, both in temperate conifer forest plantation and in tropical rain forest. On regular slope, this effect is easily corrected, although the topographic mask affects data. On irregular topography, corrected and uncorrected LAIs strongly differ, suggesting a need for reference measurements; corrected figures appear nevertheless realistic and normality is reached only for corrected values. LAIs should systematically be corrected for slope above 15-20 degrees, more so if topography is irregular or the forest cover heterogeneous.

Executive function oculomotor tasks in girls with ADHD.

OBJECTIVE: To assess executive function in girls with attention-deficit/hyperactivity disorder (ADHD) using oculomotor tasks as possible trait markers for neurobiological studies. METHOD: Thirty-two girls aged 6 to 13 years with DSM-IV ADHD and 20 age-matched, normal control girls were tested on a variety of oculomotor tasks requiring attention, working memory, and response inhibition, which included smooth pursuit, delayed response, and go-no go tasks. RESULTS: Girls with ADHD performed the delayed response task correctly on 32% of trials as measured by number of memory-guided saccades, in contrast to 62% of trials for control subjects (p = .0009). Patients made twice as many commission errors to no go stimuli (p = .0001) and 3 times as many intrusion errors (saccades in the absence of go or no go stimuli; p = .004) during the go-no go task compared with controls. Smooth pursuit performance was statistically equivalent across subject groups. Repeated testing in a subgroup of 15 patients revealed substantial practice effects on go-no go performance. CONCLUSIONS: The data confirm that girls with ADHD exhibit impairments in executive function, as has been reported in boys, implying a similar pathophysiology of ADHD in both sexes. However, practice effects may limit the utility of the oculomotor go-no go task for some neurobiological studies.

Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis.

We report a missense mutation in the gap junction protein beta-3 (encoding Connexin 31), which was detected in only the affected members of a family in which the autosomal dominant skin disease erythrokeratoderma variabilis was segregating. The nucleotide change results in an arginine to proline substitution in codon 42. This residue is positioned on the first transmembrane/first extracellular domain of the gap junction protein with the mutation replacing a negatively charged residue with a nonpolar residue. This change may disrupt the conformation of the protein and voltage gating polarity leading to impaired channel function.

ADHD in girls: clinical comparability of a research sample.

OBJECTIVE: The investigation of attention-deficit/hyperactivity disorder (ADHD) in girls raises complex questions of referral bias and selection criteria. The authors sought to determine whether they could recruit a research sample of comparably affected girls using a combination of sex-independent diagnostic criteria and sex-normed cutoffs on teacher ratings. They also report on the largest placebo-controlled crossover comparison of methylphenidate and dextroamphetamine in girls with ADHD. METHOD: Subjects were 42 girls with DSM-III-R/DSM-IV ADHD (combined type) contrasted to 56 previously studied boys with ADHD on comorbid diagnoses, behavioral ratings, psychological measures, psychiatric family history, and stimulant drug response. RESULTS: Girls with ADHD were statistically indistinguishable from comparison boys on nearly all measures. Girls exhibited robust beneficial effects on both stimulants, with nearly all (95%) responding favorably to one or both drugs in this short-term trial. Dextroamphetamine produced significantly greater weight loss than methylphenidate. CONCLUSIONS: This highly selected group of ADHD girls was strikingly comparable with comparison boys on a wide range of measures. The results confirm that girls with ADHD do not differ from boys in response to methylphenidate and dextroamphetamine and that both stimulants should be tried when response to the first is not optimal.

Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses.

Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family, adoption, and twin studies suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding, and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD. We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls, did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD.

Characterization of acellular dermal matrices (ADMs) prepared by two different methods.

The efficacy of acellular dermal matrix (ADM) in the treatment of full-thickness skin injuries as a dermal substitute depends on its low antigenicity, capacity for rapid vascularization, and stability as a dermal template. These properties will be determined largely by the final composition of the ADM. We have treated human skin with either Dispase followed by Triton X-100 detergent or NaCl followed by SDS detergent, cryosectioned the resulting ADMs, and then characterized them immunohistochemically. Staining for cell-associated antigens (HLA-ABC, HLA-DR, vimentin, desmin, talin), extracellular matrix components (chondroitin sulfate, fibronectin, laminin, vitronectin, hyaluronic acid), elastin, and collagen type VII was dramatically reduced or absent from ADMs prepared by both methods. However, significant amounts of elastin, keratan sulfate, laminin, and collagen types III and IV were still observed in both ADMs. Both methods of ADM preparation resulted in extensive extraction of both cellular and extracellular components of the skin but retention of the basic dermal architecture. In general, ADM prepared by the NaCl-SDS method retained larger amounts of each antigen than did that prepared by the Dispase-Triton method. This was most evident for laminin and type VII collagen but larger amounts of type IV collagen, fibronectin, desmin, elastin, and HLA-DR were also evident in the NaCl-SDS ADM.

Sweetener preference among non-institutionalized older adults.

The purpose of this study is to determine the ability of a group of older adults to distinguish between a new artificial sweetener (Sweet One) and sucrose and to determine a sweetener preference among older adults. Participants (n = 112), 56-90 yrs. sampled a plain low-fat blended cottage cheese and iced tea sweetened with either sucrose or Sweet One arranged in a triangle test format. Participants also sampled four low-fat vanilla puddings sweetened with sucrose, Equal, Sweet'n Low, and Sweet One and ranked them according to preference. Results show participants are able to tell the difference between sucrose and the new artificial sweetener Sweet One in the iced tea drinks. Rank order results show this sample preferred Equal and sucrose as sweeteners. The ability to taste sweetness remains high in aging. Enhancing sweetness without added calories would aid nutritional well being of the elderly.

Nursing care delivery models in ambulatory oncology.

Oncology nurse leaders are challenged to design ambulatory nursing care delivery models that are cost-effective, efficient, and facilitate positive patient outcomes. Many of the models used in the inpatient setting can be adapted to the ambulatory setting. Whatever model is implemented, it is important to delineate practice expectations.

Modeling physical therapy clinical research centers.

Because the establishment of physical therapy clinical research centers (PTCRCs) has been of interest to the profession, this project was undertaken to (1) assess the available resources, (2) complete a systems analysis, and (3) apply the results of a Delphi survey to the resulting clinical research center models. The methodology included several techniques. First, a questionnaire that addressed the status and elements of organization of PTCRCs was distributed to 118 academic institutions and 22 other facilities. A systems analysis of clinical research centers supported by various institutes at the National Institutes of Health was then completed. A Delphi procedure was also used to query a panel of physical therapy researchers regarding the components of a PTCRC. Site visits were conducted at three facilities to assess the possibility of those facilities becoming PTCRCs. From the data derived via these methods, models for PTCRCs were developed. Results showed that as many as 40 facilities reported the capability of becoming a PTCRC, but the data also showed that only four sites had extensively contributed by means of publication in peer-reviewed journals. The Delphi survey produced a number of items regarding characteristics and foci on which consensus was reached. Considering all the data, several models for PTCRCs were developed. Allowance for diversity in the structure and focus of PTCRCs appears to be a critical factor if the development of PTCRCs is to be encouraged.

A new approach to preparing students for academic medicine.

Critical thinking and self-directed learning by students are goals strongly endorsed by medical educators. Teaching medical interviewing and physical diagnosis skills is one of the most important tasks in medical school. An elective for fourth-year students was designed to address both areas. Ten senior medical students spent one month with a teaching staff member and fellow in general medicine. Part of the course was designed for independent problem-solving posed by sophisticated medical problems encountered in a general medicine practice. Skills in problem formulation, reading and assessing the medical literature, and communicating with peers were learned or improved. In the remainder of this course five pairs of senior students precepted 28 randomly chosen second-year students and taught medical interviewing and physical diagnosis. Techniques of teaching and basic pathophysiology were reviewed, and role-playing, feedback, demonstration and role-modelling were used.