Effect of e-learning and repeated performance feedback on spirometry test quality in family practice: a cluster trial

PURPOSE Spirometry has become an indispensable tool in primary care to exclude, diagnose, and monitor chronic respiratory conditions, but the quality of spirometry tests in family practices is a reason for concern. Aim of this study was to investigate whether a combination of e-learning and bimonthly performance feedback would improve spirometry test quality in family practices in the course of 1 year.METHODS Our study was a cluster trial with 19 family practices allocated to intervention or control conditions through minimization. Intervention consisted of e-learning and bimonthly feedback reports to practice nurses. Control practices received only the joint baseline workshop. Spirometry quality was assessed by independent lung function technicians. Two outcomes were defined, with the difference between rates of tests with 2 acceptable and repeatable blows being the primary outcome and the difference between rates of tests with 2 acceptable blows being the secondary outcome. We used multilevel logistic regression analysis to calculate odds ratios (ORs) for an adequate test in intervention group practices.RESULTS We analyzed 1,135 tests. Rate of adequate tests was 33% in intervention and 30% in control group practices (OR = 1.3; P=.605). Adequacy of tests did not differ between groups but tended to increase with time: OR = 2.2 (P = .057) after 3 and OR = 2.0 (P = .086) in intervention group practices after 4 feedback reports. When ignoring test repeatability, these differences between the groups were slightly more pronounced: OR = 2.4 (P = .033) after 3 and OR=2.2 (P = .051) after 4 feedback reports.CONCLUSIONS In the course of 1 year, we observed a small and late effect of e-learning and repeated feedback on the quality of spirometry as performed by family practice nurses. This intervention does not seem to compensate the lack of rigorous training and experience in performing spirometry tests in most practices.     

Integrin‐Linked Kinase Regulates Bone Formation by Controlling Cytoskeletal Organization and Modulating BMP and Wnt Signaling in Osteoprogenitors

Cell‐matrix interactions constitute a fundamental aspect of skeletal cell biology and play essential roles in bone homeostasis. These interactions are primarily mediated by transmembrane integrin receptors, which mediate cell adhesion and transduce signals from the extracellular matrix to intracellular responses via various downstream effectors, including integrin‐linked kinase (ILK). ILK functions as adaptor protein at focal adhesion sites, linking integrins to the actin cytoskeleton, and has been reported to act as a kinase phosphorylating signaling molecules such as GSK‐3β and Akt. Thereby, ILK plays important roles in cellular attachment, motility, proliferation and survival. To assess the in vivo role of ILK signaling in osteoprogenitors and the osteoblast lineage cells descending thereof, we generated conditional knockout mice using the Osx‐Cre:GFP driver strain. Mice lacking functional ILK in osterix‐expressing cells and their derivatives showed no apparent developmental or growth phenotype, but by 5 weeks of age they displayed a significantly reduced trabecular bone mass, which persisted into adulthood in male mice. Histomorphometry and serum analysis indicated no alterations in osteoclast formation and activity, but provided evidence that osteoblast function was impaired, resulting in reduced bone mineralization and increased accumulation of unmineralized osteoid. In vitro analyses further substantiated that absence of ILK in osteogenic cells was associated with compromised collagen matrix production and mineralization. Mechanistically, we found evidence for both impaired cytoskeletal functioning and reduced signal transduction in osteoblasts lacking ILK. Indeed, loss of ILK in primary osteogenic cells impaired F‐actin organization, cellular adhesion, spreading, and migration, indicative of defective coupling of cell‐matrix interactions to the cytoskeleton. In addition, BMP/Smad and Wnt/β‐catenin signaling was reduced in the absence of ILK. Taken together, these data demonstrate the importance of integrin‐mediated cell‐matrix interactions and ILK signaling in osteoprogenitors in the control of osteoblast functioning during juvenile bone mass acquisition and adult bone remodeling and homeostasis. © 2017 American Society for Bone and Mineral Research.     

Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery

Purpose

To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA).

Methods

Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied.

Results

The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin.

Conclusion

Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.

     

Non-oncology physician visits after diagnosis of cancer in adolescents and young adults

Purpose

Health care needs of adolescents and young adults (AYAs) with cancer are probably different from other age groups. Studying their non-oncology physician visits in the first years after diagnosis may provide insight into the specific health problems AYA patients experience and thereby help to improve care for these patients.

Methods

Seven hundred seventy-four AYAs identified from a Canadian provincial registry diagnosed with cancer between ages 15 and 24 years in 1991/2001 were included, matched by birth year and sex to ten controls. Based on provincial health insurance plan records, we determined the number of family physician and non-cancer specialist visits in the 5 years after diagnosis (for patients) or inclusion (for controls).

Results

The percentage of patients visiting a non-cancer specialist decreased from 96 to 49 % over the 5-year period. The percentage visiting a family physician decreased from 96 to 84 %. Visits in all years were significantly higher than among controls. In the first year after diagnosis, many patients visited a non-cancer specialist or a family physician for neoplasm-related health problems (77 and 55 %, respectively). In addition, family physicians were also consulted for general age-specific problems, such as genitourinary symptoms

Conclusions

In the first years after diagnosis of cancer in AYAs, both non-cancer specialist and family physician visits are common, although non-cancer specialist visits are less common and decline considerably faster than in younger children.

Implications for Cancer Survivors

The specific pattern of physician visits of this age group calls for care that is tailored to their specific needs.

     

Early trabecular bone healing around titanium implants: a histologic study in rabbits

BACKGROUND: A detailed insight into the early healing response of trabecular bone to unloaded titanium implants is lacking. METHODS: Cylindrical implants were inserted in the tibial epiphysis of rabbits and left to heal for 1 to 42 days. Samples were processed into paraffin or methylmethacrylate sections and histomorphometrically analyzed. RESULTS: A hematoma was observed after 1 and 3 days of implant placement. In addition, small fragments of bone trabeculae were detected around the implant as a result of the implant installment procedure. Soon, osteoclasts were observed resorbing these fragments, whereas osteoblasts incorporated them in strands of new bone, thereby making them difficult to distinguish from day 7 onward. At that time, osteoblasts were detected at the edges of the preexisting bone, actively depositing new bone, resulting in maximal osteoid deposition around the implant after 28 days (58%). After 7 days of healing, the presence of basic remodeling units in the surrounding bone was already maximal (P <0.05 versus t = 1 and 3 days). This remodeling activity, together with the new bone formation, provided a firm anchoring of the implant in the trabecular bone. CONCLUSIONS: This study evaluated the early cellular events in trabecular bone surrounding titanium implants. The insertion of an implant into bone initiates a series of biologic processes, including the formation of a hematoma, shattered bone fragments adjacent to the implantation site, intensive bone remodeling, and the formation of new bone, eventually leading to the osseointegration of the implant.     

Tetrasomy 9p due to an intrachromosomal triplication of 9p13-p22

To date, approximately 30 patients have been described with a tetrasomy 9p, all being caused by the presence of an isochromosome 9p. We now report on a 3-year-old boy with a de novo intrachromosomal triplication of 9p13-p22, resulting in partial tetrasomy 9p. We compared his phenotype with cases of tetrasomy 9p caused by the presence of an extra isochromosome 9p. He has facial anomalies similar to those of cases of tetrasomy 9p, central nervous system abnormalities, and severe psychomotor retardation but no other major congenital anomalies. Fluorescence in situ hybridization with region-specific probes showed that the middle repeat of the triplicated part is inverted. Microsatellite analysis demonstrated an involvement of both paternal chromosome 9 homologues in the triplication. This is compatible with either unequal crossing over of three of the four chromatids in paternal meiosis I or with a double crossing over in meiosis I and II (or an early mitotic division). Am. J. Med. Genet. 86:168–173, 1999. © 1999 Wiley-Liss, Inc.