Management of type 2 diabetes using non-insulin glucose-lowering therapies: a critical appraisal of clinical practice guidelines with the AGREE II instrument.

AIM: Type 2 diabetes is a major global epidemic affecting over 400 million people worldwide. The objective of this systematic review was to provide an overview of recommendations from clinical practice guidelines (guidelines) addressing non-insulin based pharmacological management of among non-pregnant adults in an outpatient setting, and critically appraise their methodological development. METHODS: We systematically searched MEDLINE and Embase databases, for relevant guidelines using the Ovid interface. We scanned the bibliographies of all eligible guidelines for additional relevant citations. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and appraised the reporting quality of guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE II) instrument. RESULTS: Our search yielded 11264 unique citations, of which 124 were retrieved for full-text review; 17 guidelines proved eligible. The highest scoring AGREE domain was 'clarity of presentation' (66%; range 7-92%), followed by 'scope and purpose' (58%; range 25-92%), 'editorial independence' (55%; range 0-91%), 'stakeholder involvement' (45%; range 11-90%) and 'rigour of development' (43%; range 4-92%). The poorest domain was 'applicability' (37%; range 6-84%). The guidelines authored by the World Health Organization group achieved the highest AGREE overall score. CONCLUSIONS: Most of the guidelines provided recommendations with a local jurisdictional focus and showed significant variation in the quality. Nevertheless, only a small number of those scored well overall.

The value of the 24-h delayed abdominal radiograph of barium enema in the diagnosis of Hirschsprung's disease.

AIM OF STUDY: The objective of this study is to determine the diagnostic value of the 24-h delayed film for Hirschsprung's disease (HD). Other features of the barium enema were also examined, in particular the correlation between the radiological transition zone (TZ) and the final pathology. METHODS: All patients with suspected HD from 2003 to 2013 who had undergone barium enema and rectal biopsy were reviewed retrospectively to study the correlation between radiological features of barium enema with the final diagnosis as well as severity. RESULTS: A total of 182 patients were admitted for suspected HD during the study period, of which 82 had both investigations done. 68 patients had radiological features suggestive of the disease and ultimately, 12 patients had the disease confirmed with rectal biopsy. Among those without radiological features of HD, 2 patients were found to have the disease. Thus, the sensitivity of the 24-h delayed film was 85.7 % and the specificity was 17.6 %. The positive predictive value (PPV) of this test was 20.6 % and the negative predictive value (NPV) was 85.7 %. Regarding the level of TZ, it was not detected in the barium enema in 7 (50 %) out of the 14 patients. For those with the presence of TZ, 6 (85.7 %) of them correlated well with the intra-operative findings and 4 (57.1 %) of them correlated well with the final histology. CONCLUSION: The 24-h delayed film of barium enema has a high NPV and is useful to rule out HD. However, rectal biopsy is still suggested for disease confirmation given its low PPV. Lastly, once present, the level of radiological TZ is also a useful predictor for the actual disease involvement.

Heyde's syndrome: diagnosis and management by the novel single-balloon enteroscopy.

We present a case of obscure gastro-intestinal bleeding due to small bowel angiodysplasia in a 68-year-old woman with severe aortic valve stenosis. The diagnosis was confirmed and subsequently managed using single-balloon enteroscopy.

Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite.

Recently, strontium (Sr) as ranelate compound has become increasingly popular in the treatment of osteoporosis. However, the lattice structure of bone crystal after Sr incorporation is yet to be extensively reported. In this study, we synthesized strontium-substituted hydroxyapatite (Sr-HA) with different Sr content (0.3%, 1.5% and 15% Sr-HA in mole ratio) to simulate bone crystals incorporated with Sr. The changes in chemical composition and lattice structure of apetite after synthetic incorporation of Sr were evaluated to gain insight into bone crystal changes after incorporation of Sr. X-ray diffraction (XRD) patterns revealed that 0.3% and 1.5% Sr-HA exhibited single phase spectrum, which was similar to that of HA. However, 15% Sr-HA induced the incorporation of HPO4(2-) and more CO3(2-), the crystallinity reduced dramatically. Transmission electron microscopy (TEM) images showed that the crystal length and width of 0.3% and 1.5% Sr-HA increased slightly. Meanwhile, the length and width distribution were broadened and the aspect ratio decreased from 10.68+/-4.00 to 7.28+/-2.80. The crystal size and crystallinity of 15% Sr-HA dropped rapidly, which may suggest that the fundamental crystal structure is changed. The findings from this work indicate that current clinical dosage which usually results in Sr incorporation of below 1.5% may not change chemical composition and lattice structure of bone, while it will broaden the bone crystal size distribution and strengthen the bone.

Characteristics and mechanical properties of acrylolpamidronate-treated strontium containing bioactive bone cement.

The aim of the present study was to determine the influence of surface treatment on the mechanical properties of strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement. Previously we developed an injectable bioactive cement (SrHAC) system composed of Sr-HA powders and bisphenol A diglycidylether dimethacrylate (Bis-GMA). In this study, the Sr-HA powder was subjected to surface treatment using acrylolpamidronate, a bisphosphonate derivative, which has a polymerizable group, to improve the interface between inorganic filler and organic matrix by binding Sr-HA and copolymerizing into the matrix. After surface treatment, the compression strength, bending strength, and stiffness of the resulting composites were defined by using a material testing machine (MTS) according to ISO 5833. The fracture surface of the bone cement specimen was observed with a scanning electron microscope. Invitro cytotoxicity of surface-treated SrHAC was also studied using a tetrazolium-based cell viability assay (MTS/pms) on human osteoblast-like cells, the SaOS-2 cell line. Cells were seeded at a density of 10(4)/mL and allowed to grow in an incubator for 48 h at 37 degrees C. Results indicated that after surface treatment, the compression strength and stiffness significantly improved by 22.68 and 14.51%, respectively. The bending strength and stiffness of the bioactive bone cement also showed 19.06 and 8.91% improvements via three-point bending test. The fracture surface micromorphology after compression and bending revealed that the bonding between the resin to surface-treated filler considerably improved. The cell viability indicated that the treated particles were nontoxic and did not inhibit cell growth. This study demonstrated a new surface chemistry route to enhance the covalent bonds between inorganic fillers and polymer matrix for improving the mechanical properties of bone cement. This method not only improves the overall mechanical performance but also increases osteoblastic activity.

Biocompatibility of electrophoretical deposition of nanostructured hydroxyapatite coating on roughen titanium surface: in vitro evaluation using mesenchymal stem cells.

A nano hydroxyapatite (HAp) layer was coated on a roughen titanium surface by means of electrophoretic deposition with an acetic anhydride solvent system. The objectives of this current study are to investigate whether nano-HAp can improve mechanical strength at a lower sintering temperature and biocompatibility. Densification temperature was lowered from usual 1000 to 800 degrees C. The coating interfacial bonding strength, phase purity, microstructure, and biocompatibility were investigated. Degradation of HA phase was not detected in XRD. A porous TiO2 layer acts as a gradient coating layer with an intermediate thermal expansion coefficient between hydroxyapatite and titanium that reduces the thermal stress. From SEM image, the coating does not contain any crack. Mesenchymal stem cell (MSC) is the progenitor cell for various tissues in mature animals, which can improve integration of bone tissue into implant. In this in vitro study, rabbit MSCs culture indicated that the HAp/Ti nanocomposite biomaterial had good biocompatibility and bioactivity. Around materials and on its surface cell grew well with good morphology. Proliferation of the MSCs on the nano-HAp coating was higher than its micron counterpart in XTT assay. These properties show potential for the orthopaedic and dental applications.

A magnetic resonance imaging study of iron overload in hemopoietic stem cell transplant recipients with increased ferritin levels.

We performed a study of magnetic resonance imaging (MRI) assessment of hemosiderosis in the heart (T2/T2*), liver (T2*), pancreas (T2*), and pituitary gland (T2/T2*/SIR) in 20 hemopoietic stem cell transplant (HSCT) recipients (median peak ferritin levels 7615 pmol/L, range 3411 to 33000 pmol/L). MRI reading was abnormal in the heart (5%), liver (85%), pancreas (40%), and pituitary gland (55%). The heart T2 correlated with peak ferritin levels (P=.024), while the liver T2* correlated with current ferritin (P=.038) values only. Pancreatic T2* values correlated with pituitary T2 and signal intensity ratio values. The ejection fraction was abnormal in 10% of cases and did not correlate with ferritin level or heart T2. The peak liver enzymes correlated with peak ferritin (P=.025), but the current liver enzymes were mostly normal. Pancreatic assessments (fasting glucose, insulin, beta cell function, insulin reserve, and C-peptide) and pituitary growth hormone axis assessments (growth hormone, insulin growth factor-1, and insulin growth factor binding protein-3) were abnormal in 40% to 70% of cases. They were unrelated to pancreas or pituitary MRI values. Interestingly, endocrine assessments correlated with heart T2 values and peak (but not current) ferritin levels. We concluded that iron overload may contribute to organ damage after HSCT, and MRI assessment may be useful in its detection and treatment monitoring.

Interfacial behaviour of strontium-containing hydroxyapatite cement with cancellous and cortical bone.

The bone-bonding behaviors of various biomaterials have been extensively investigated. However, the precise mechanisms of bone bonding have not yet been clarified, and the differences in interfacial behaviors of biomaterial bonding with cancellous bone and cortical bone have not yet been understood. In this study, strontium-containing hydroxyapatite (Sr-HA) cement, in which 10% calcium ions were substituted by strontium, was performed in a rabbit hip replacement model. Six months later, the morphology and chemical composition of interfaces between Sr-HA cement with cancellous bone and cortical bone were evaluated by field emission scanning electron microscopy (FESEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Remarkable differences between these two interfaces were suggested both in morphology and chemical compositions. An apatite layer was found between Sr-HA cement and cancellous bone with a thickness of about 70 microm. However, only a very thin interface (about 1 microm) was formed with cortical bone. As for the cancellous bone/cement interface, high ions intensity of Ca, P, Sr, Na, and O were confirmed by FESEM-EDX and ToF-SIMS. Differences in morphology and chemical component between these two interfaces provided convincing evidences for the proposed dissolution-precipitation coupling mechanism in the formation of biological apatite.

Strontium-containing hydroxyapatite bioactive bone cement in revision hip arthroplasty.

Clinical outcome of cemented implants to revision total hip replacement (THR) is not as satisfactory as primary THR, due to the loss of bone stock and normal trabecular pattern. This study evaluated a bioactive bone cement, strontium-containing hydroxyapatite (Sr-HA) bone cement, in a goat revision hip hemi-arthroplasty model, and compared outcomes with polymethylmethacrylate (PMMA) bone cement. Nine months after operation, significantly higher bonding strength was found in the Sr-HA group (3.36+/-1.84 MPa) than in the PMMA bone cement group (1.23+/-0.73 MPa). After detached from the femoral component, the surface of PMMA bone cement mantle was shown relatively smooth, whereas the surface of the Sr-HA bioactive bone cement mantle was uneven, by SEM observation. EDX analysis detected little calcium and no phosphorus on the surface of PMMA bone cement mantle, while high content of calcium (14.03%) and phosphorus (10.37%) was found on the surface of the Sr-HA bone cement mantle. Even higher content of calcium (17.37%) and phosphorus (10.84%) were detected in the concave area. Intimate contact between Sr-HA bioactive bone cement and bone was demonstrated by histological and SEM observation. New bone bonded to the surface of Sr-HA cement and grew along its surface. However, fibrous tissue was observed between PMMA bone cement and bone. The results showed good bioactivity of Sr-HA bioactive bone cement in this revision hip replacement model using goats. This in vivo study also suggested that Sr-HA bioactive bone cement was superior to PMMA bone cement in terms of bone-bonding strength. Use of bioactive bone cement may be a possible solution overcoming problems associated with the use of PMMA bone cement in revision hip replacement.

Strontium exerts dual effects on calcium phosphate cement: Accelerating the degradation and enhancing the osteoconductivity both in vitro and in vivo.

Calcium phosphate cements (CPCs) have long been used as osteoconductive bone substitutes in the treatment of bone defects. However, the degradation rate of CPC is typically too slow to match the new bone growth rate. It is known that strontium increases the solubility of hydroxyapatite as well as exerts both anabolic and anticatabolic effects on bone. Therefore, we hypothesized that the incorporation of strontium would accelerate the degradation rate and enhance the osteoconductivity of CPC. In this study, Three groups, CPC (0% Sr-CPC), 5% Sr-CPC, and 10% Sr-CPC, were prepared, with the total molar ratio for Sr/(Sr+Ca) in the cement powder phase being 0, 5, and 10%, respectively. In the immersion test, less residual weight was observed in both 5% Sr-CPC and 10% Sr-CPC groups than CPC group. In addition, a higher osteoblastic cell proliferation rate and alkaline phosphatase activity were obtained in the strontium groups. In a rat femur bone defect model comparing CPC with 10% Sr-CPC, at 2 weeks postoperation, early endochondral ossification was found in the 10% Sr-CPC group, whereas only fibrous tissue was observed in control group; at 4-16 weeks postoperation, progressive osteoconduction toward the cement was observed in both groups. At 32 weeks, a higher peri-cement bone area and reduced cement area were noted in the 10% Sr-CPC group. In conclusion, in the 10% Sr-CPC group, strontium exerts dual effects on CPC: accelerating degradation rate and enhancing osteoconductivity, as shown here both in vitro and in vivo.

Comparison of one-day oral dosing with three bismuth compounds for the suppression of Helicobacter pylori assessed by the 13C-urea breath test.

Assessment of intragastric urease activity by the 13C-urea breath test was performed before and after one day of dosing with either De-Noltabs (tripotassium dicitrato bismuthate, one tablet 1 q.d.s.), Pepto-Bismol liquid (bismuth salicylate 30 ml q.d.s.), or Roter tablets (bismuth subnitrate, one tablet q.d.s.) in twelve Helicobacter pylori-positive patient volunteers. There was a significant decrease in the excess of 13CO2 after one day of dosing with each of the three bismuth compounds, but analysis of variance could detect no difference between the effects of the three compounds. Systemic absorption of bismuth following oral dosing with either Pepto-Bismol or Roter is minimal, yet both compounds have a suppressive effect on H. pylori similar to that of De-Noltab. This study suggests that the action of all three bismuth compounds is within the gastric lumen, and that systemic absorption of bismuth is not necessary for activity against H. pylori.

A rare site and appearance for lymphomatous recurrence.

A patient with a recurrence of large cell lymphoma is reported. There was psoas muscle involvement, which showed ring enhancement post-intravenous contrast on CT scan. Ring enhancement in skeletal muscle infiltration by lymphoma has not been described previously.

An error concealment algorithm for images subject to channel errors.

We present an algorithm to conceal bit errors in still images and image sequences that are coded using the discrete cosine transform (DCT) and variable length codes (VLCs). No modification is necessary to an existing encoder, and no additional bit rate is required. The concealment algorithm is kept simple so that real-time decoding and concealment is possible. A single bit error in these images can cause a block to split into several blocks or several blocks to merge into one. This causes the DCT coefficients of all subsequent blocks to be correctly decoded but stored in the wrong location in the image. Furthermore, the DC coefficient of all subsequent blocks may be incorrect. The error concealment algorithm uses transform domain information to identify the location of the affected blocks and to correct errors. The image quality after error concealment is shown to be significantly improved.

Metabolic control of diabetes in a diabetes centre.

OBJECTIVE: To examine the effectiveness of a diabetes centre in restoring metabolic control in patients with poorly controlled diabetes. DESIGN: Retrospective review of medical records. SETTING: Diabetes centre of a district hospital, Hong Kong. PARTICIPANTS: Patients with poorly controlled diabetes referred to a diabetes centre. MAIN OUTCOME MEASURES: Primary endpoints were mean change in glycated haemoglobin levels and the number of patients who achieved glycated haemoglobin levels of 7.0% or lower, 7.5% or lower, and 8.0% or lower, respectively. Complementary endpoints were serial changes in body weight, blood pressure, and lipids. RESULTS: One hundred and eighty-five patients, predominantly with type 2 diabetes (94.6%), were reviewed. Median duration since diagnosis of diabetes was 8 years (interquartile range, 4.3-11.8 years). Seventy-three patients had a body mass index of 25 kg/m(2) or higher. The baseline and latest glycated haemoglobin levels were 10.4% (standard deviation, 2%) and 8.2% (1.4%), respectively; mean reduction was 2.2% (95% confidence interval, 1.9-2.5; P<0.0005). Eighty-one patients were discharged after a median 32 weeks of follow-up. Their mean glycated haemoglobin level on discharge was 7.5% (0.8%), and the mean reduction was 2.8% (95% confidence interval, 2.4-3.3; P<0.0005). The cumulative percentages of discharged patients who achieved glycated haemoglobin levels of less than 7.0%, 7.5%, and 8.0% were 30.9%, 53.1%, and 77.8%, respectively. Newly diagnosed diabetes (P=0.006) was the only factor which predicted a favourable glycaemic response. CONCLUSION. The Diabetes Centre provided effective management for a heterogeneous group of patients referred with poorly controlled diabetes.

An effective approach by a chelate reaction in optimizing the setting process of strontium-incorporated calcium phosphate bone cement.

Strontium (Sr) plays a special role in enhancing the biological osteo-stimulation of calcium phosphate cement (CPC), not only increasing osteoblast-related gene expression and the alkaline phosphatase (ALP) activity of mesenchymal stem cells (MSCs), but also inhibiting the differentiation of osteoclasts. However, the incorporation of Sr unfortunately delays the setting of CPC and weakens its mechanical properties. The purpose of this study was to overcome the aforementioned problems by introducing a chelate reaction between Ca/Sr cations from the original solid phases and carboxyl groups from the liquid phases. As expected, the setting process of Sr-incorporated CPC was optimized and the cement body after rapid hardening was mostly consisting of unreacted original solid phases. After soaking in simulated body fluid for 14 and 28 days, the composition of the cement body gradually converted to the most thermodynamic stable phase, hydroxyapatite, indicating an in vitro bioactivity. The compressive strength was not impaired in the Sr-incorporated groups, but rather, further increased over time. Higher cell proliferation rate and better ALP activity of MG-63 cells cultured on the cement surface were obtained with the presence of Sr content, demonstrating potential abilities to favor new bone formation.

In Vitro characterization of low modulus linoleic acid coated strontium-substituted hydroxyapatite containing PMMA bone cement.

Poly (methyl methacrylate) (PMMA) bone cement is widely used in vertebral body augmentation procedures such as vertebroplasty and balloon kyphoplasty. Filling high modulus PMMA increases the modulus of filled verterbra, increasing the risk of fracture in the adjacent vertebra. On the other hand, in porous PMMA bone cements, wear particle generation and deterioration of mechanical performance are the major drawbacks. This study adopts a new approach by utilizing linoleic acid coated strontium substituted hydroxyapatite nanoparticle (Sr-5 HA) and linoleic acid as plasticizer reducing bone cement's modulus with minimal impact on its strength. We determined the compressive strength (UCS) and modulus (Ec), hydrophobicity, injectability, in vitro bioactivity and biocompatibility of this bone cement at different filler and linoleic acid loading. At 20 wt % Sr5-HA incorporation, UCS and Ec were reduced from 63 ± 2 MPa, 2142 ± 129 MPa to 58 ± 2 MPa, 1785 ± 64 MPa, respectively. UCS and Ec were further reduced to 49 ± 2 MPa and 774 ± 70 MPa respectively when 15 v/v of linoleic acid was incorporated. After 7 days of incubation, pre-osteoblast cells (MC3T3-E1) attached on 20 wt % Sr5-HA and 20 wt % Sr5-HA with 15 v/v of linoleic acid group were higher (3.73 ± 0.01 x 104, 2.27 ± 0.02 x 104) than their PMMA counterpart (1.83 ± 0.04 x 104). Incorporation of Sr5-HA with linoleic acid in monomer phase is more effective in reducing the bone cement's stiffness than Sr5-HA alone. Combination of low stiffness and high mechanical strength gives the novel bone cement the potential for use in vertebroplasty cement applications.

Strontium borate glass: potential biomaterial for bone regeneration.

Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones.

Solubility of strontium-substituted apatite by solid titration.

Solid titration was used to explore the solubility isotherms of partially (Srx-HAp, x=1, 5, 10, 40, 60 mol.%) and fully substituted strontium hydroxyapatite (Sr-HAp). Solubility increased with increasing strontium content. No phase other than strontium-substituted HAp, corresponding to the original titrant, was detected in the solid present at equilibrium; in particular, dicalcium hydrogen phosphate was not detected at low pH. The increase in solubility with strontium content is interpreted as a destabilization of the crystal structure by the larger strontium ion. Carbonated HAp was formed in simulated body fluid containing carbonate on seeding with Sr10-HAp, but the precipitate was strontium-substituted on seeding with Sr-HAp. Strontium-substituted HAp might be usable as a template for the growth of new bone, since nucleation appears to be facilitated.

Mechanical properties and in vitro response of strontium-containing hydroxyapatite/polyetheretherketone composites.

Strontium-containing hydroxyapatite/polyetheretherketone (Sr-HA/PEEK) composites were developed as alternative materials for load-bearing orthopaedic applications. The amount of strontium-containing hydroxyapatite (Sr-HA) incorporated into polyetheretherketone (PEEK) polymer matrix ranged from 15 to 30 vol% and the composites were successfully fabricated by compression molding technique. This study presents the mechanical properties and in vitro human osteoblast-like cell (MG-63) response of the composite material developed. The bending modulus and strength of Sr-HA/PEEK composites were tailored to mimic human cortical bone. PEEK reinforced with 25 and 30 vol% Sr-HA exhibited bending modulus of 9.6 and 10.6 GPa, respectively; alternatively, the bending strengths of the composites were 93.8 and 89.1 MPa, respectively. Based on the qualitative comparison of apatite formation in SBF and quantitative measurement of MG-63-mediated mineralization in vitro, the Sr-HA/PEEK composite was proven to outperform HA/PEEK in providing bioactivity. However, no difference was found in the trend of cell proliferation and alkaline phosphatase activity between different composites. Strontium, in the form of strontium-containing hydroxyapatite (Sr-HA), was confirmed to enhance bioactivity in the PEEK composites.