Assessment by finite element analysis of the impact of osteoporosis and osteoarthritis on hip resurfacing

Hip resurfacing is proposed as an alternative to total hip replacement (THR) for treatment of osteoarthritis (OA), especially for younger, heavier and more active sufferers. There is however, concern with regards to the incidence of post operative femoral neck fractures. We have investigated, with finite element models, the changes in stress and strain in the femoral neck following hip resurfacing. We have included several different bone material property values representing normal, elderly, osteoarthritic and osteoporotic bone. We have also modelled two different hip implant orientations. We have shown that hip resurfacing may increase the magnitude of stress and strain in the femoral neck, especially in osteoporotic bone. We have also shown that the superolateral offset associated with the valgus orientation, not the valgus orientation itself, may be what reduces the stress and strain in the neck and leads to lower incidence of fracture

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Background: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Objective: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin. Sources: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK). Funding: The National Institute for Health Research Health Technology Assessment programme

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Do Nonsteroidal Anti-Inflammatory Drugs Cause Endoprosthetic Loosening? Mid- to Long-Term Follow-Up of 100 Total Hip Arthroplasties after Local NSAID Infiltration

We evaluated the effect of local infiltration of NSAIDs on prosthetic fixation at mid- to long-term follow-up of total hip arthroplasties. Intra-articular local NSAID (ketorolac) was injected into hip joints and surrounding tissues intraoperatively and postoperatively as a part of multimodal pain management protocol. Clinical and radiographic evaluation was performed for any evidence of component loosening or failure and clinical outcomes in 100 total hip joint arthroplasties with a mean follow-up of 7.3 years (4.9 to 11 yrs). Radiographic analysis at the most recent follow-up showed no evidence of loosening, subsidence, or migration and no evidence of impending failure. Clinical outcomes showed improved Harris hip scores. Intra-articular NSAID used in the intraoperative/postoperative period in hip arthroplasty showed no evidence of prosthetic loosening at mid- to long-term follow-up

Targeting and dissolution characteristics of bone forming and antibacterial drugs by harnessing the structure of microspherical shells from coral beach sand

Pharmaceutical drugs for the treatment of metabolic bone diseases lead to a number of side effects due to the their uncontrollable dispersion throughout the body.1 Therefore, many groups directed their research to develop devices that are targeted to specific organs or tissues and release the encapsulated drug in a highly regulated way.2-7 The development of completely resorbable bone-filling biomaterials delivering drugs would offer a therapeutic approach of drug release and bone augmentation in a simple one-step process.8-11 The biomaterials selected needs custom designs, to control the quantity and the duration of drug release and at the same time inducing desirable host cell responses and preventing bacterial infection.12-15 Current synthetic biomaterials produced as drug delivery microspheres due to production difficulties contain not very well designed interconnected pores and fail to fill these pertinent requirements. Turning directly to nature such as marine structures for inventive solutions can help to solve these problems due to their structure, chemistry and architecture and their unique designs.16-20 We demonstrate -for the first time- the potential of unique coral shells with specific microspherical structure and highly organised interconnected intra-pore designs to offer a number of desired functions for targeted delivery of Bisphosphonate (BP) (paminodrate) and an antibiotic (Gentamicin) for bone regeneration, repair and preventive antibacterial slow drug delivery. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Reflective interferometric gas sensing using nanoporous anodic aluminium oxide (AAO)

Abstract not availableTushar Kumeria and Dusan Losi