Management of prediabetes from the perspective of Spanish physicians and community pharmacists: Detecta2 study.

INTRODUCTION: Prediabetes is a high-risk state for diabetes. The study aims to describe routine clinical practice and the views of physicians and pharmacists on prediabetes management. MATERIALS AND METHODS: An observational, descriptive, cross-sectional study was conducted using a structured questionnaire. RESULTS: A total of 410 physicians and 393 pharmacists completed the questionnaire. Self-adherence to clinical practice guidelines (CPGs) was reported by 51.5% and 23.2% of physicians and pharmacists, respectively. Less than 60% of participants defined prediabetes according to main CPG. Regarding the use of screening strategies to detect prediabetes (physicians: 96%; pharmacists: 42.1%), reports indicate the opportunistic strategy is widely employed (≥75%) whereas systematic screening is unusual (<20%). Changes in lifestyle were deemed essential by almost all participants (≥95%), but in clinical practice only 58.3% of healthcare centers and 28.0% of pharmacies were found to provide awareness-raising/instruction. The role of pharmacists in the prevention of prediabetes/diabetes was judged useful by most participants. CONCLUSIONS: Use of CPG, systematic prediabetes screening strategies, and specific strategies for patient education are scarce. The support of community pharmacists in prediabetes management was well valued. Therefore, it is crucial that the lines of action followed by both physicians and pharmacists align with each other and with the CPG.

Management of prediabetes from the perspective of Spanish physicians and community pharmacists: Detecta2 study.

INTRODUCTION: Prediabetes is a high-risk state for diabetes. The study aims to describe routine clinical practice and the views of physicians and pharmacists on prediabetes management. MATERIALS AND METHODS: An observational, descriptive, cross-sectional study was conducted using a structured questionnaire. RESULTS: A total of 410 physicians and 393 pharmacists completed the questionnaire. Self-adherence to clinical practice guidelines (CPGs) was reported by 51.5% and 23.2% of physicians and pharmacists, respectively. Less than 60% of participants defined prediabetes according to main CPG. Regarding the use of screening strategies to detect prediabetes (physicians: 96%; pharmacists: 42.1%), reports indicate the opportunistic strategy is widely employed (≥75%) whereas systematic screening is unusual (<20%). Changes in lifestyle were deemed essential by almost all participants (≥95%), but in clinical practice only 58.3% of healthcare centers and 28.0% of pharmacies were found to provide awareness-raising/instruction. The role of pharmacists in the prevention of prediabetes/diabetes was judged useful by most participants. CONCLUSIONS: Use of CPG, systematic prediabetes screening strategies, and specific strategies for patient education are scarce. The support of community pharmacists in prediabetes management was well valued. Therefore, it is crucial that the lines of action followed by both physicians and pharmacists align with each other and with the CPG.

Breakthrough cancer pain treatment in Spain: physicians' perception of current opioids utilization and prescription.

Objectives: Multiple reasons for suboptimal treatment of breakthrough cancer pain (BTcP) have been reported in the literature. We aimed to ascertain the perception of physicians on the potential inappropriate use and prescription of rapid-onset opioids (ROOs) for breakthrough cancer pain (BTcP) and the causes thereof.Methods: Observational study based on an online survey addressed to doctors from different specialties (radiation oncology, medical oncology, anesthesia, palliative care and general practitioners) with experience in the management of BTcP in the Spanish public health setting.Results: A total of 114 eligible specialists mainly from radiation oncology (37.7%), medical oncology (24.6%) and pain units (18.4%) participated in the study. Most agreed on important aspects of BTcP management, such as their preference for ROOs or the need for early follow-up after treatment initiation. However, their answers revealed a lack of standardization of BTcP diagnosis. Half of respondents believed that their BTcP patients might misuse ROOs. Physicians polled believed that lack of training in pain management (71.9%) and inadequate BTcP diagnosis and evaluation (66.7%) were the greatest obstacles for prescribing opioids. Specialists also thought that they do not provide the necessary information to patients (51.8%) and caregivers (57.9%) to guarantee the correct use of these drugs.Conclusions: These results are of utmost importance as they highlight the need to increase physicians' awareness of BTcP and its management and the need to improve communication with patients and their caregivers. Our findings also indicate the need for future research on the possible misuse of opioids in BTcP patients and its causes.

Oncogenic K-ras segregates at spatially distinct plasma membrane signaling platforms according to its phosphorylation status.

Activating mutations in the K-Ras small GTPase are extensively found in human tumors. Although these mutations induce the generation of a constitutively GTP-loaded, active form of K-Ras, phosphorylation at Ser181 within the C-terminal hypervariable region can modulate oncogenic K-Ras function without affecting the in vitro affinity for its effector Raf-1. In striking contrast, K-Ras phosphorylated at Ser181 shows increased interaction in cells with the active form of Raf-1 and with p110α, the catalytic subunit of PI 3-kinase. Because the majority of phosphorylated K-Ras is located at the plasma membrane, different localization within this membrane according to the phosphorylation status was explored. Density-gradient fractionation of the plasma membrane in the absence of detergents showed segregation of K-Ras mutants that carry a phosphomimetic or unphosphorylatable serine residue (S181D or S181A, respectively). Moreover, statistical analysis of immunoelectron microscopy showed that both phosphorylation mutants form distinct nanoclusters that do not overlap. Finally, induction of oncogenic K-Ras phosphorylation - by activation of protein kinase C (PKC) - increased its co-clustering with the phosphomimetic K-Ras mutant, whereas (when PKC is inhibited) non-phosphorylated oncogenic K-Ras clusters with the non-phosphorylatable K-Ras mutant. Most interestingly, PI 3-kinase (p110α) was found in phosphorylated K-Ras nanoclusters but not in non-phosphorylated K-Ras nanoclusters. In conclusion, our data provide - for the first time - evidence that PKC-dependent phosphorylation of oncogenic K-Ras induced its segregation in spatially distinct nanoclusters at the plasma membrane that, in turn, favor activation of Raf-1 and PI 3-kinase.