Aims: Therapeutic inertia, defined as the failure to initiate or intensify therapy in a timely manner according to evidence‐based clinical guidelines, is a key reason for uncontrolled hyperglycaemia in patients with type 2 diabetes. The aims of this systematic review were to identify how therapeutic inertia in the management of hyperglycaemia was measured and to assess its extent over the past decade. Materials and Methods: Systematic searches for articles published from January 1, 2004 to August 1, 2016 were conducted in MEDLINE and Embase. Two researchers independently screened all of the titles and abstracts, and the full texts of publications deemed relevant. Data were extracted by a single researcher using a standardized data extraction form. Results: The final selection for the review included 53 articles. Measurements used to assess therapeutic inertia varied across studies, making comparisons difficult. Data from low‐ to middle‐income countries were scarce. In most studies, the median time to treatment intensification after a glycated haemoglobin (HbA1c) measurement above target was more than 1 year (range 0.3 to >7.2 years). Therapeutic inertia increased as the number of antidiabetic drugs rose and decreased with increasing HbA1c levels. Data were mainly available from Western countries. Diversity of inertia measures precluded meta‐analysis. Conclusions: Therapeutic inertia in the management of hyperglycaemia in patients with type 2 diabetes is a major concern. This is well documented in Western countries, but corresponding data are urgently needed in low‐ and middle‐income countries, in view of their high prevalence of type 2 diabetes.

The therapeutic and toxic effects of drugs are often generated through effects on distinct cell types in the body. Selective delivery of drugs to specific cells or cell lineages would, therefore, have major advantages, in particular, the potential to significantly improve the therapeutic window of an agent. Cells of the monocyte-macrophage lineage represent an important target for many therapeutic agents because of their central involvement in a wide range of diseases including inflammation, cancer, atherosclerosis, and diabetes. We have developed a versatile chemistry platform that is designed to enhance the potency and delivery of small-molecule drugs to intracellular molecular targets. One facet of the technology involves the selective delivery of drugs to cells of the monocyte-macrophage lineage, using the intracellular carboxylesterase, human carboxylesterase-1 (hCE-1), which is expressed predominantly in these cells. Here, we demonstrate selective delivery of many types of intracellularly targeted small molecules to monocytes and macrophages by attaching a small esterase-sensitive chemical motif (ESM) that is selectively hydrolyzed within these cells to a charged, pharmacologically active drug. ESM versions of histone deacetylase (HDAC) inhibitors, for example, are extremely potent anticytokine and antiarthritic agents with a wider therapeutic window than conventional HDAC inhibitors. In human blood, effects on monocytes (hCE-1-positive) are seen at concentrations 1000-fold lower than those that affect other cell types (hCE-1-negative). Chemical conjugates of this type, by limiting effects on other cells, could find widespread applicability in the treatment of human diseases where monocyte-macrophages play a key role in disease pathology.

4-Deoxy-4,4-difluoro-glycosides have been synthesised for the first time via a direct sequence involving ring-closing metathesis and indium-mediated difluoroallylation with 1-bromo-1,1-difluoropropene in water. Two protecting group strategies were explored, one to allow protection of the primary C-6 hydroxyl group throughout the sequence, while the second was intended to allow deprotection after RCM and before dihydroxylation. The benzyl ether could be used in the first role, and pivaloyl is effective in the second. Dihydroxylations were highly stereoselective and controlled by the orientation of the glycosidic C–O bond.

The copper-catalysed zinc phosphonate chemistry described by Yokomatsu and Shibuya can be used to enter the classical organometallic coupling repertoire via Stille and Suzuki–Miyaura couplings. 1,4-Diiodobenzene underwent coupling with the organozinc reagent derived from diethyl bromodifluoromethylphosphonate with copper(I) catalysis to afford diethyl (4-iodophenyl)difluoromethylphosphonate. Higher yielding couplings were run with (4-trifluoromethylsulfonyloxy)- and (4-nonafluorobutylsulfonyloxy)-iodobenzenes. The iodide and the triflate coupled under palladium-catalysed conditions with a range of stannanes and boronic acids in moderate to excellent yields. Shibuya–Yokomatsu couplings were also successful with more functionalised iodoarenes and heteroarenes presenting the important phosphate mimic on a range of scaffolds.

Poor adherence to statins increases cardiovascular disease risk. We systematically identified 32 controlled studies that assessed patient-centered interventions designed to improve statin adherence. The limited number of studies and variation in study characteristics precluded strict quality criteria or meta-analysis. Cognitive education or behavioural counselling delivered face-to-face multiple times consistently improved statin adherence compared with control groups (7/8 and 3/3 studies, respectively). None of four studies using medication reminders and/or adherence feedback alone reported significantly improved statin adherence. Single interventions that improved statin adherence but were not conducted face-to-face included cognitive education in the form of genetic test results (two studies) and cognitive education via a website (one study). Similar mean adherence measures were reported for 17 intervention arms and were thus compared in a sub-analysis: 8 showed significantly improved statin adherence, but effect sizes were modest (+7 to +22 % points). In three of these studies, statin adherence improved despite already being high in the control group (82–89 vs. 57–69 % in the other studies). These three studies were the only studies in this sub-analysis to include cognitive education delivered face-to-face multiple times (plus other interventions). In summary, the most consistently effective interventions for improving adherence to statins have modest effects and are resource-intensive. Research is needed to determine whether modern communications, particularly mobile health platforms (recently shown to improve medication adherence in other chronic diseases), can replicate or even enhance the successful elements of these interventions while using less time and fewer resources.

A very short reaction sequence opens with metal-mediated addition of commercial bromodifluoropropene to aldehydes; allylation under phase transfer catalysed conditions sets the stage for a ring closing metathesis (RCM) in the presence of commercial Grubbs’ catalyst to afford potentially useful difluorinated dihydropyrans.