Feasibility of a musculoskeletal ultrasound intervention to improve adherence in juvenile idiopathic arthritis: a proof-of concept trial

Background

Non-adherence is a prevalent and modifiable issue in juvenile idiopathic arthritis (JIA) that currently lacks provider-based intervention. Education surrounding disease status is one way in which families remain engaged in their care. Musculoskeletal ultrasound is one such form of demonstrative, real-time education that may impact the way patients and caregivers self-manage their disease. The aims of this study are to 1) assess the feasibility, acceptability and perceived usefulness of musculoskeletal ultrasound as a non-adherence intervention tool and 2) to examine changes in methotrexate adherence in adolescents with JIA following the ultrasound.

Methods

Eight adolescents with polyarticular or extended oligoarticular JIA and their caregivers completed this 12?week study. A within subject design was used to compare baseline and post-intervention adherence, quality of life and disease activity indices. Adherence measures included electronic measurement of methotrexate in addition to self-reported adherence questionnaires. The ultrasound intervention included a one-time, rheumatologist provided, educational examination of three or more currently or historically active joints.

Results

The ultrasound intervention was found to be both feasible and acceptable. One hundred percent of eligible participants completed the ultrasound intervention. The ultrasound was well received by patients and caregivers, with most believing this to be a helpful tool. Baseline adherence was 75.3% among participants, with half of the participants being classified as non-adherent. Electronically measured and self-reported adherence measures did not show significant changes during the post-intervention period. Two participants improved, four participants maintained, and two participants decreased adherence. On ultrasound, 18/27 (66.7%) of the examined joints displayed abnormalities, with 63% being discrepant and additive to the rheumatologist’s physical examination.

Conclusions

While our intervention did not show any changes in adherence, quality of life or disease activity indices in this proof-of-concept trial, the intervention does show promise in acceptability measures and merits future study in a more robust trial design. An additional study benefit was that the musculoskeletal ultrasound intervention was able to demonstrate subclinical disease, leading to clinically impactful therapeutic changes in several participants.

     

Diabetes beyond insulin: review of new drugs for treatment of diabetes mellitus

Diabetes mellitus (DM) is a progressive disease characterized by insulin deficiency and insulin resistance or both. The fasting and post-prandial blood glucose is elevated, exposing the patient to acute and chronic complications (micro- and macro-vascular) leading to blindness, kidney failure, heart disease, stroke and amputations. Improving glycemic control has been demonstrated to lower the risk of these complications. Owing to the progressive nature of the disease, an evolving treatment strategy is necessary to maintain glycemic control. Varieties of new pharmacologic interventions are developed in past 5 years to treat people with diabetes. Several studies have been carried out covering different aspects of pharmacological interventions (newer and old drugs) along with the effects of weight loss, diet and exercise. Two categories of drugs have been used for the treatment of Diabetes Mellitus: the insulin and oral agents. Insulin analogues are molecules that differ from human insulin in amino acid sequence but bind to the insulin receptors and act similarly in function. This article provides an update of pharmacologic interventions for diabetes with practical overview of the new drug options, new insulin analogues, pharmacology, clinical efficacy, safety, dosing, cost, with specific examples of each and their background and side effects used to achieve tight glucose control. These agents have distinct characteristics that help in their selection for the treatment of type 1 and type 2 diabetes.     

Current surgical treatment of squamous cell carcinoma of the head and neck

Historically treatment of head and neck cancers involved surgical resection followed by radiation therapy for advanced tumors. Concurrent chemoradiation therapies have shown equal survival to surgical resection with better preservation of function. However, concurrent therapy does entail significant morbidity, and recent advances have been used to minimize that morbidity. Newer tumor specific medical therapies are anticipated to be less toxic while maintaining a high degree of efficacy. For resectable cancer, transoral laser microsurgery is a new trend in surgery for complete resection of tumors with preservation of function. Advanced reconstructive techniques that allow free transfer of soft tissue and bone from all over the body improve the functional and aesthetic outcomes following major ablative surgery. With successful surgical reconstruction, dental and prosthetic rehabilitation choices are enhanced. Advances in rehabilitation of speech following removal of the larynx have improved the quality of life post-laryngectomy patients. With these newer therapies and methods of reconstruction, each patient needs to be carefully evaluated to maximize the possibility of cure and level of function, and minimize the morbidity associated with treatment. Combined chemotherapy and radiation protocols are associated with increased acute and chronic toxicities that may affect the quality of life due to the impact upon oral disease and oral function. Oral care providers must be aware of advances in cancer management and implications for patient care to effectively care for these patients.     

Scrotal extension of emphysematous pyelonephritis

We report an extensive form of emphysematous pyelonephritis (EPN) in the right kidney extending from the anterior abdominal wall to the scrotum in a patient with renal calculi with obstructive uropathy and describe the progression route of infection from retroperitoneum to scrotum. Such an extensive occurrence of EPN is very rare. The patient succumbed after 48 h despite aggressive treatment.     

Congenitally unguarded tricuspid valve orifice with a hypoplastic right ventricle and free thrombus in a giant right atrium

Patients with congenitally unguarded tricuspid valve orifice, along with associated abnormalities, rarely survive till adulthood. We report such a case, with a hypoplastic right ventricle and a floating thrombus in a giant right atrium, with intact interatrial and interventricular septa. The patient was managed surgically with satisfactory outcome.     

Green primaries: environmentally friendly energetic complexes

Primary explosives are used in small quantities to generate a detonation wave when subjected to a flame, heat, impact, electric spark, or friction. Detonation of the primary explosive initiates the secondary booster or main-charge explosive or propellant. Long-term use of lead azide and lead styphnate as primary explosives has resulted in lead contamination at artillery and firing ranges and become a major health hazard and environmental problem for both military and civilian personnel. Devices using lead primary explosives are manufactured by the tens of millions every year in the United States from primers for bullets to detonators for mining. Although substantial synthetic efforts have long been focused on the search for greener primary explosives, this unresolved problem has become a "holy grail" of energetic materials research. Existing candidates suffer from instability or excessive sensitivity, or they possess toxic metals or perchlorate. We report here four previously undescribed green primary explosives based on complex metal dianions and environmentally benign cations, (cat)(2)[M(II)(NT)(4)(H(2)O)(2)] (where cat is NH(4)(+) or Na(+), M is Fe(2+) or Cu(2+), and NT(-) is 5-nitrotetrazolato-N(2)). They are safer to prepare, handle, and transport than lead compounds, have comparable initiation efficiencies to lead azide, and offer rapid reliable detonation comparable with lead styphnate. Remarkably, they possess all current requirements for green primary explosives and are suitable to replace lead primary explosives in detonators. More importantly, they can be synthesized more safely, do not pose health risks to personnel, and cause much less pollution to the environment.     

Green primary explosives: 5-nitrotetrazolato-N2-ferrate hierarchies

The sensitive explosives used in initiating devices like primers and detonators are called primary explosives. Successful detonations of secondary explosives are accomplished by suitable sources of initiation energy that is transmitted directly from the primaries or through secondary explosive boosters. Reliable initiating mechanisms are available in numerous forms of primers and detonators depending upon the nature of the secondary explosives. The technology of initiation devices used for military and civilian purposes continues to expand owing to variations in initiating method, chemical composition, quantity, sensitivity, explosive performance, and other necessary built-in mechanisms. Although the most widely used primaries contain toxic lead azide and lead styphnate, mixtures of thermally unstable primaries, like diazodinitrophenol and tetracene, or poisonous agents, like antimony sulfide and barium nitrate, are also used. Novel environmentally friendly primary explosives are expanded here to include cat[Fe(II)(NT)(3)(H(2)O)(3)], cat(2)[Fe(II)(NT)(4)(H(2)O)(2)], cat(3)[Fe(II)(NT)(5)(H(2)O)], and cat(4)[Fe(II)(NT)(6)] with cat = cation and NT(-) = 5-nitrotetrazolato-N(2). With available alkaline, alkaline earth, and organic cations as partners, four series of 5-nitrotetrazolato-N(2)-ferrate hierarchies have been prepared that provide a plethora of green primaries with diverse initiating sensitivity and explosive performance. They hold great promise for replacing not only toxic lead primaries but also thermally unstable primaries and poisonous agents. Strategies are also described for the systematic preparation of coordination complex green primaries based on appropriate selection of ligands, metals, and synthetic procedures. These strategies allow for maximum versatility in initiating sensitivity and explosive performance while retaining properties required for green primaries.     

A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine

PURPOSE To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies. PATIENTS AND METHODS In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety. Results Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%). CONCLUSION T-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population.