High value, cost-conscious care: An international imperative

Health care costs in the United States are the highest in the world, and are continuing to rise at a level that is unsustainable. However, although this problem is more acute in the United States than elsewhere in the world, it is a challenge for all nations to control the costs of health care. The high cost of health care in the U.S. is not accompanied by a higher quality of care, but rather is related in large measure to health system "waste" that does not benefit patients but adds to cost. Representing approximately 30% of dollars spent on health care, this waste includes a significant amount of money spent on overuse and misuse of diagnostic testing, including screening tests. The American College of Physicians, the largest specialty society for physicians in the U.S., representing internal medicine and all of its subspecialties, has embarked upon a High Value, Cost-Conscious Care initiative, aimed at identifying areas of overuse and misuse of care, and leading to development of guidelines, educational materials, and other resources targeted to health care providers, trainees, and the general public. It is incumbent upon physicians, non-physician health care professionals, patients, and other health care stakeholders to address the issue of reducing care that is not appropriate, both to improve the overall quality of care and to reduce the associated unsustainable financial burden to society.     

CLT1 targets angiogenic endothelium through CLIC1 and fibronectin

Angiogenesis is important for tumor growth and metastasis. CLT1 (CGLIIQKNEC), a peptide that binds to tumor interstitial spaces in the presence of fibrin-fibronectin, has structural similarity to the anti-angiogenic β-sheet peptides anastellin and anginex. This similarity is reflected in the ability of CLT1 to form co-aggregates with fibronectin that induce an unfolded protein response and cause autophagic cell death in proliferating endothelial cells. CLT1 cytotoxicity is mediated at least in parts by a novel CLT1 binding protein, Chloride Intracellular Channel 1 (CLIC1), which promotes internalization of CLT1-fibronectin co-aggregates in a mechanism that depends on the LIIQK amino acid sequence of CLT1. LIIQK encompasses amino acid residues relevant for CLT1 binding to CLIC1 and in addition, facilitates the formation of CLT1-fibronectin co-aggregates, which in turn promote translocation of CLIC1 to the endothelial cell surface through ligation of integrin αvβ3. Paralleling the in vitro results, we found that CLT1 co-localizes with CLIC1 and fibronectin in angiogenic blood vessels in vivo, and that CLT1 treatment inhibited angiogenesis and tumor growth. Our findings show that CLT1 is a new anti-angiogenic compound, and its mechanism of action is to form co-aggregates with fibronectin, which bind to angiogenic endothelial cells through integrins, become internalized through CLIC1 and elicit a cytotoxic unfolded protein response. The simple structure and high potency of CLT1 make it a potentially useful compound for anti-angiogenic treatments.     

Subcutaneous chronic implantable defibrillation systems in humans

The recent introduction of subcutaneous implantable cardioverter defibrillator (S-ICD) has raised attention about the potential of this technology for clinical use in daily clinical practice. We review the methods and results of the four studies conducted in humans for approval of this innovative technology for daily practice. Two studies using a temporary S-ICD system (acute human studies) were conducted to search for an appropriate lead configuration and energy requirements. For this purpose, 4 S-ICD configurations were tested in 78 patients at the time of transvenous (TV)-ICD implantation. The optimal configuration was tested in 49 more patients to comparatively assess the subcutaneous defibrillation threshold (S-DFT) versus the standard TV-ICD. Long-term implants were evaluated in 55 patients using an implanted system (chronic human study). The acute humans studies led to an optimal S-ICD configuration comprising a parasternal electrode and left anterolateral thoracic pulse generator. Both configurations successfully terminated 98% of induced ventricular fibrillation (VF), but significantly higher energy levels were required with S-ICD than with TV-ICD systems (36.6?±?19.8 J vs. 11.1?±?8.5 J). In the chronic study, all 137 VF episodes induced at time of implant were detected with a 98% conversion rate. Two pocket infections and four lead revisions were required during 10?±?1 months of follow-up. During this period, survival was 98%, and 12 spontaneous ventricular tachyarrhythmias were detected and treated by the device. These data show that the S-ICD systems here consistently detected and converted VF induced at time of implant as well as sustained ventricular tachyarrhythmias occurring during follow-up (248).     

Pumpers, skypers, surfers and texters: technology to improve the management of diabetes in teenagers

A variety of innovative technologies are available to assist with the management of diabetes in teenagers. Technologies include devices that assist with the direct day-to-day management of diabetes including insulin pumps and continuous glucose monitors. These devices are being used more and more with teenagers as a means of improving treatment adherence and glycaemic control. In addition, telehealth is being used to deliver care and support around diabetes management issues for teens with diabetes. Telehealth used in diabetes care for teens includes cell phones and video-conferencing. The goal of this telehealth technology is to support health behaviours and implement behavioural change strategies in a way that is more integrated into the everyday lives of patients and even in the context in which the behaviours occur in 'real time'. Finally, information and support via the Internet are gaining acceptance and use among teens with diabetes as an effective means of strategies for improved diabetes self-care. All three of these broad uses of technology in diabetes in teens represent flexible, innovative, and accessible approaches to improving both diabetes management and glycaemic control in this 'at risk' population.     

Circumoral complications in hereditary sensory and autonomic neuropathy — a case of simple lip reconstruction?

We report a case of a 7-year-old Bangladeshi boy who caused himself oral incontinence by self-mutilation. The patient was known to suffer from hereditary sensory and autonomic neuropathy type V. As definitive management, a full dental clearance was performed along with reconstruction of the lower lip with a good functional and aesthetic outcome. He did not experience any adverse effects from the full dental clearance with regard to feeding, nutrition or development. We discuss the dilemma and challenges raised in the management of this patient and highlight the need for a multi-disciplinary specialist input for what appeared to be a simple case of lip reconstruction for a plastic surgeon.     

(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors

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