Functionalization of α-hydroxyphosphonates as a convenient route to N-tosyl-α-aminophosphonates

Direct conversion of the α-hydroxyl group by para-toluenesulfonamide to yield α-(N-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b–37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b–21a,b in the presence of K₂CO₃, via the retro-Abramov reaction of the appropriate aldehydes, 1–5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b–37a,b with better diastereoselectivity than in the case of the Pudovik reaction. The mechanism for this transformation is proposed herein. When Cbz N-protected aziridine 9a,b and phenylalanine analogue 12a,b were exploited, intramolecular substitution was observed, leading to the corresponding epoxide 38 as the sole product, or oxazolidin-2-one 39 as a minor product. Analogous substitution was not observed in the case of proline 18a,b and serine 21a,b derivatives.

The reaction mechanism and diastereoselectivity of the direct transformation of α-hydroxyphosphonates 6a,b–21a,b by para-toluenesulfonamide, yielding α-(N-tosyl)aminophosphonates 23a,b–37a,b under K₂CO₃ conditions are presented.     

Implementation of selective prevention for cardiometabolic diseases; are Dutch general practices adequately prepared?

Objective: Current guidelines acknowledge the need for cardiometabolic disease (CMD) prevention and recommend five-yearly screening of a targeted population. In recent years programs for selective CMD-prevention have been developed, but implementation is challenging. The question arises if general practices are adequately prepared. Therefore, the aim of this study is to assess the organizational preparedness of Dutch general practices and the facilitators and barriers for performing CMD-prevention in practices currently implementing selective CMD-prevention.

Design: Observational study.

Setting: Dutch primary care.

Subjects: General practices.

Main outcome measures: Organizational characteristics.

Results: General practices implementing selective CMD-prevention are more often organized as a group practice (49% vs. 19%, p?=?.000) and are better organized regarding chronic disease management compared to reference practices. They are motivated for performing CMD-prevention and can be considered as ‘frontrunners’ of Dutch general practices with respect to their practice organization. The most important reported barriers are a limited availability of staff (59%) and inadequate funding (41%).

Conclusions: The organizational infrastructure of Dutch general practices is considered adequate for performing most steps of selective CMD-prevention. Implementation of prevention programs including easily accessible lifestyle interventions needs attention. All stakeholders involved share the responsibility to realize structural funding for programmed CMD-prevention. Aforementioned conditions should be taken into account with respect to future implementation of selective CMD-prevention.

• Key Points

• There is need for adequate CMD prevention. Little is known about the organization of selective CMD prevention in general practices.

• ??The organizational infrastructure of Dutch general practices is adequate for performing most steps of selective CMD prevention.

• ??Implementation of selective CMD prevention programs including easily accessible services for lifestyle support should be the focus of attention.

• ??Policy makers, health insurance companies and healthcare professionals share the responsibility to realize structural funding for selective CMD prevention.

     

Evaluating the change in central corneal thickness in neonates (term and preterm) in Indian population and the factors affecting it

Background and Aim:

Central corneal thickness (CCT) of term and preterm infants in Indian population is not known. We did a prospective noninterventional study to measure the CCT in term and preterm infants.

Materials and Methods:

An ultrasonic pachymeter was used. The data regarding the date of birth, expected date of delivery, birth weight were recorded. The preterm and the term infants were followed up at 8 weeks, 20 weeks and at 1-year.

Results:

A total of 85 (170 eyes) children were included in the study. The mean age was 264.6 ± 21.8 days postconception. The mean birth weight and CCT were 1834.4 ± 512.1 g and 595.8 ± 72.4 μ respectively. A comparison of CCT on the basis postgestational age showed a mean thickness of 620.7 ± 88.8 and 574.4 ± 78.3 μ in the <260 days and >260 days age groups respectively. The difference was statistically significant (Student''s test, P = 0.002). The CCT of preterm infants (<260 days) decreased from a mean value of 620.7 ± 88.8 μ to 534.1 ± 57.6 μ at the end of 1-year.

Conclusion:

We present the data of CCT in term and preterm infants in Indian population. We believe that the premature babies have slightly thicker corneas than mature term babies.     

Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban

Background. Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban. Methods. A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared. Results. All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62–0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results. Conclusion. The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.     

Role of prothrombin 19911 A>G polymorphism,blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

Journal of Thrombosis and Thrombolysis - The role of the A&gt;G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism...