Real-world evidence studies into treatment adherence, thresholds for intervention and disparities in treatment in people with type 2 diabetes in the UK.

Purpose: The University of Surrey-Lilly Real World Evidence (RWE) diabetes cohort has been established to provide insights into the management of type 2 diabetes mellitus (T2DM). There are 3 areas of study due to be conducted to provide insights into T2DM management: exploration of medication adherence, thresholds for changing diabetes therapies, and ethnicity-related or socioeconomic-related disparities in management. This paper describes the identification of a cohort of people with T2DM which will be used for these analyses, through a case finding algorithm, and describes the characteristics of the identified cohort.

Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia.

Seven young patients with X-linked hypophosphatemia (XLH, having inactivating PHEX mutations) were discovered to accumulate osteopontin (OPN) at the sites of defective bone mineralization near osteocytes - the so-called hallmark periosteocytic (lacunar) "halos" of XLH. OPN was also localized in the pericanalicular matrix extending beyond the osteocyte lacunae, as well as in the hypomineralized matrix of tooth dentin. OPN, a potent inhibitor of mineralization normally degraded by PHEX, is a member of a family of acidic, phosphorylated, calcium-binding, extracellular matrix proteins known to regulate dental, skeletal, and pathologic mineralization.

Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660).

In 1985, we briefly reported infant sisters with a unique, lethal, autosomal recessive disorder designated congenital sclerosing osteomalacia with cerebral calcification. In 1986, this condition was entered into Mendelian Inheritance In Man (MIM) as osteomalacia, sclerosing, with cerebral calcification (MIM 259660). However, no attestations followed.

Acute cardiac decompensation in a patient with beta-thalassemia and diabetes mellitus following cessation of chelation therapy.

Patients with higher liver iron stores are likely to have a worse cardiac outcome following noncompliance with chelation. Cardiovascular magnetic resonance identifies myocardial siderosis allowing optimization of iron chelation regimes. Diabetes puts thalassemic patients at increased risk of myocardial fibrosis.

Embrained drives to perform extraordinary roles predict schizotypal traits in the general population.

Some personal drives correspond to extraordinary social roles. Given that behavioral strategies associated with such drives may conflict with those associated with ordinary roles, they could cause behavioral disorganization. To test whether they do so independent of the factors responsible for full-blown schizotypy and schizophrenia, these drives were assessed in the general population.

Asfotase alfa therapy for children with hypophosphatasia.

Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss.

Differential Effects of p38, MAPK, PI3K or Rho Kinase Inhibitors on Bacterial Phagocytosis and Efferocytosis by Macrophages in COPD.

Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD.

Significantly greater triglyceridemia in Black African compared to White European men following high added fructose and glucose feeding: a randomized crossover trial.

Background: Black African (BA) populations are losing the cardio-protective lipid profile they historically exhibited, which may be linked with increasing fructose intakes. The metabolic effects of high fructose diets and how they relate to blood lipids are documented for Caucasians, but have not been described in BA individuals.

Objective: The principle objective of this pilot study was to assess the independent impacts of high glucose and fructose feeding in men of BA ancestry compared to men of White European (WE) ancestry on circulating triglyceride (TG) concentrations.

Skeletal Fluorosis Due To Inhalation Abuse of a Difluoroethane-Containing Computer Cleaner.

Skeletal fluorosis (SF) is endemic in many countries and millions of people are affected worldwide, whereas in the United States SF is rare with occasional descriptions of unique cases. We report a 28-year-old American man who was healthy until 2 years earlier when he gradually experienced difficulty walking and an abnormal gait, left hip pain, loss of mobility in his right wrist and forearm, and progressive deformities including enlargement of the digits of both hands. Dual-energy X-ray absorptiometry (DXA) of his lumbar spine, femoral neck, total hip, and the one-third forearm revealed bone mineral density (BMD) Z-scores of +6.

Bariatric Surgery in Obese Women of Reproductive Age Improves Conditions That Underlie Fertility and Pregnancy Outcomes: Retrospective Cohort Study of UK National Bariatric Surgery Registry (NBSR).

Background: The aims of this study are the following: to describe the female population of reproductive age having bariatric surgery in the UK, to assess the age and ethnicity of women accessing surgery, and to assess the effect of bariatric surgery on factors that underlie fertility and pregnancy outcomes.

Methods: Demographic details, comorbidities, and operative type of women aged 18-45 years were extracted from the National Bariatric Surgery Registry (NBSR). A comparison was made with non-operative cases (aged 18-45 and BMI ≥40 kg/m) from the Health Survey for England (HSE, 2007-2013).

Option generation in the treatment of unstable patients: An experienced-novice comparison study.

There are a dearth of studies that quantitatively measure nurses' appreciation of stimuli and the subsequent generation of options in practice environments. The purpose of this paper was to provide an examination of nurses' ability to solve problems while quantifying the stimuli upon which they focus during patient care activities. The study used a quantitative descriptive method that gathered performance data from a simulated task environment using multi-angle video and audio.

Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen.

Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments.

ADULT HYPOPHOSPHATASIA TREATED WITH TERIPARATIDE: REPORT OF 2 PATIENTS AND REVIEW OF THE LITERATURE.

Objective: Hypophosphatasia (HPP) is a rare inherited metabolic bone disease from deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Reportedly, teriparatide (parathyroid hormone 1-34) can benefit the adult form of HPP, including fracture healing. We studied 2 women with adult HPP given teriparatide and reviewed the reports of 6 additional patients.

Idiopathic Acquired Osteosclerosis in a Middle-Aged Woman With Systemic Lupus Erythematosus.

Widely distributed osteosclerosis is an unusual radiographic finding with multiple causes. A 42-year-old premenopausal Spanish woman gradually acquired dense bone diffusely affecting her axial skeleton and focally affecting her proximal long bones. Systemic lupus erythematosus (SLE) diagnosed in adolescence had been well controlled.

Systematic review of adherence rates by medication class in type 2 diabetes: a study protocol.

Introduction: Treatment options for type 2 diabetes are becoming increasingly complex with people often prescribed multiple medications, and may include both oral and injectable therapies. There is ongoing debate about which drug classes provide the optimum second-line and third-line treatment options. In the real world, patient adherence and persistence determines medication effectiveness.

Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment.

Hypophosphatasia is the inborn error of metabolism characterized by low serum alkaline phosphatase activity (hypophosphatasaemia). This biochemical hallmark reflects loss-of-function mutations within the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). TNSALP is a cell-surface homodimeric phosphohydrolase that is richly expressed in the skeleton, liver, kidney and developing teeth.

Insulin detemir may be less efficacious in patients with nonalcoholic fatty liver disease and hypertriglyceridemia.

Insulin detemir is commonly used in obese patients with diabetes mellitus as it is considered hepatoselective and causes less weight gain. We describe a relative lack of effectiveness of detemir in patients with significant NAFLD and hypertriglyceridemia, compared to isophane insulin. This may affect how such patients are managed with insulin.

Outcomes of Implementing an Evidence-Based Hypertension Clinical Guideline in an Academic Nurse Managed Health Center.

This column shares the best evidence-based strategies and innovative ideas on how to facilitate the learning and implementation of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at http://onlinelibrary.wiley.

Auricular ossification: A newly recognized feature of osteoprotegerin-deficiency juvenile Paget disease.

We report auricular ossification (AO) affecting the elastic cartilage of the ear as a newly recognized feature of osteoprotegerin (OPG)-deficiency juvenile Paget disease (JPD). AO and auricular calcification refer interchangeably to rigid pinnae, sparing the ear lobe, from various etiologies. JPD is a rare Mendelian disorder characterized by elevated serum alkaline phosphatase activity accompanied by skeletal pain and deformity from rapid bone turnover.

Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9.

Congenital insensitivity to pain (CIP) comprises the rare heritable disorders without peripheral neuropathy that feature inability to feel pain. Fracturing and joint destruction are common complications, but lack detailed studies of mineral and skeletal homeostasis and bone histology. In 2013, discovery of a heterozygous gain-of-function mutation in SCN11A encoding voltage-gated sodium channel 1.