Pd-Mediated γ-C(sp3)-H Bond Activation in Ammonia-Ugi 4-CR Adducts by Using Picolinamide as Directing Group.

The development of a novel protocol for the fast introduction of the picolinamide directing group in aliphatic ketones by using the ammonia-Ugi 4-CR reaction and the subsequent evaluation of the Pd-mediated γ-C(sp3)-H bond activation is described. The methodology allows the efficient construction of a series of γ-arylated α-aminoamides bearing a congested carbon in two steps.

[Gastric non-Hodgkin lymphoma associated with heavy metal exposures]. / Linfoma no Hodgkin gástrico asociado a intoxicación por metales pesados.

Primary extranodal Non-Hodgkin lymphoma (NHL) is a non epithelial tumours that accounts for 40% of cases of NHL. Spread of nodal lymphomas to the gastrointestinal tract (GIT) is the most common location. Within the GIT is the stomach the most affected organ (60%). We report the case of 52-year- old man , mining company worker for over 10 years, which is derived to the Service of Gastroenterology with history of epigastric pain, nausea, vomiting and weight loss. Upper gastrointestinal endoscopic examination revealed an ulcerated lesion on greater curve of stomach and histopathological examination and subsequent immunohistochemical analysis showed diffuse large B cell gastric NHL. Also, the patient had multiple organ involvement in relation to chronic exposure to heavy metals, which was found in the mineralograma, with the highest concentration of uranium, thallium, arsenic, lead and mercury. The literature has described the association of chronic occupational exposure to uranium and arsenic with NHL presenting gastrointestinal involvement. Therefore, gastric commitment can not be considered as an isolated injury, but rather part of systemic involvement associated with elevated concentrations of metals. Mining is a key driver of income for Peru; however, there are no reports to date of the association of gastrointestinal NHL commitment regarding occupational exposure to heavy metals.

A retrospective analysis of therapy adherence in imatinib resistant or intolerant patients with chronic myeloid leukemia receiving nilotinib or dasatinib in a real-world setting.

OBJECTIVES: To compare adherence to second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib in patients with imatinib resistant or intolerant chronic myeloid leukemia (CML) receiving second-line therapies. METHODS: Two U.S. administrative claims databases were reviewed (January 1997 to March 2011) for CML patients previously treated with imatinib, who received ≥1 prescription of dasatinib or nilotinib and had continuous enrollment ≥1 month before and after the index date (first dasatinib or nilotinib prescription date). Medication possession ratios (MPRs) and proportion of days covered (PDCs) were evaluated between the treatment initiation date until the end of continuous eligibility, for a maximum of 12 months. Sensitivity analyses were conducted to compare patients initiated on nilotinib to patients who initiated dasatinib 100 mg/day and 140 mg/day separately. This study provides updated results of a previously published study. RESULTS: In total, 878 CML patients who received second-line treatment with either dasatinib (n = 550) or nilotinib (n = 328) were studied. Dasatinib users were less adherent compared to nilotinib users; mean MPR was 0.739 (standard deviation [SD] 0.246) for dasatinib and 0.800 (SD 0.246) for nilotinib (adjusted difference = 0.061; P = 0.002). Subgroup analyses of patients who initiated dasatinib 100 mg/day and 140 mg/day separately presented similar trends; after multivariate adjustment, adherence was 0.039 points lower in the 100 mg/day group (P = 0.034) and 0.120 points lower in the 140 mg/day group (P < 0.001). CONCLUSIONS: Among patients treated in the second-line CML setting, those treated with nilotinib had significantly higher adherence compared to patients treated with dasatinib, regardless of dasatinib dose (100 mg/day and 140 mg/day). LIMITATIONS: The study was subject to common limitations of claims data, which lack clinical information, may contain inaccuracies in diagnosis and procedure coding, and may not truly reflect actual drug consumption. Moreover, daily doses calculated based on refill records may not reflect accurate dosing regimens.

Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers.

OBJECTIVE: To compare persistence and adherence among patients with chronic obstructive pulmonary disease (COPD) treated with either multiple- or single- long-acting maintenance inhalers. METHODS: Patients with ≥2 COPD medical claims and ≥2 prescriptions for a long-acting inhaler within 1 year were classified as single- or multiple-inhaler users based on their treatment regimen (MarketScan database; 2004-2008) and matched on demographics and statistically significant baseline characteristics. Persistence, analyzed via time to treatment discontinuation, and treatment adherence, measured by proportion of days covered (PDC), were compared between the two groups over a 12-month period. Sensitivity analyses were conducted in patients with poorly and well-controlled disease. RESULTS: A total of 23,494 patients were grouped into 11,747 matched pairs. After adjusting for confounding factors, multiple-inhaler users had a significantly higher discontinuation rate [Hazard ratio = 1.40, p < 0.0001] compared with single-inhaler users. Multiple-inhaler users were less likely to be adherent than single-inhaler users with an average PDC of 0.51 (SD = 0.272) vs. 0.55 (SD = 0.279), respectively (p < 0.0001). These results were consistent for the poorly- and well-controlled disease groups. CONCLUSIONS: Multiple long-acting inhaler users demonstrated lower treatment persistence and adherence rates than single long-acting inhaler users. Limitations of the study are related to the retrospective, observational design and use of claims data.