Single-center study on features of immune mediated diseases in JAK2 (V617F)-positive myeloproliferative neoplasms and the potential therapeutic role of JAK inhibitors.

OBJECTIVE: The Janus Kinase (JAK) 2 (V617F) mutation is the most frequently detected in myeloproliferative neoplasms (MPN). JAK2(V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMIDs), thromboembolic complications or other cancers. We aimed to evaluate the prevalence and main features of both rheumatic and non-rheumatic IMIDs in a cohort of MPNs patients with JAK2 (V617F) mutation. METHODS: Study of all patients diagnosed with MPNs and JAK2 (V617F) mutation at a tertiary hospital in Northern Spain from 2004 to 2022. We focused on patients with rheumatic IMIDs to assess the time from IMIDs diagnosis to the detection of JAK2V617F mutation, the clinical course and severity of the disease, potential thrombotic complications, malignancies and therapeutic response. RESULTS: 130 patients (73 men/57 women; mean age, 70.1 ± 14.5 years) were identified. Fifty-four (41.5 %) patients were diagnosed with at least one IMID. The prevalence of rheumatic IMIDs was 7.7 % (n = 10), including rheumatoid arthritis (n = 4), polymyalgia rheumatica (n = 3), Sjögren syndrome (n = 1), antiphospholipid syndrome (n = 1) and autoinflammatory syndrome with WDR1 mutation (n = 1). Thrombotic complications were observed in 4 of these 10 patients. The clinical course of the rheumatic IMID was mild in most cases and responded to conventional immunosuppressive therapy. One patient was successfully treated with Baricitinib, a JAK1/JAK2 inhibitor. CONCLUSIONS: A high prevalence of rheumatic IMIDs is observed in patients with MPNs and JAK2 (V617F) mutation. JAK inhibitors might be a targeted therapy option in these patients.

Effectiveness of a brief motivational intervention in the management of risky alcohol use in primary care: ALCO-AP20 study protocol.

Background: Motivational interviewing (MI) could be a method for minimizing alcohol-related harm. The study aims to assess the effectiveness of a brief intervention, based on a MI, in patients with risky alcohol use attended in Primary Care (PC). Materials and methods: A cluster-randomized, two-arm parallel, multicenter, open-label, controlled clinical trial. Fifty PC healthcare professionals from the province of Córdoba (Spain) will be randomized to one of the two study groups: (1) Experimental Group (EG): MI-based approach; (2) Control Group (CG): Usual care based on health advice. EG intervention: Professionals will receive a training program focused on MI, consisting of a training workshop and the use of pre- and post-workshop questionnaires to measure knowledge and skills acquired, as well as the degree of empathy, with a videotape of the health professionals with standardized patients, before and after the workshop, and subsequent training feedback. CG intervention: Workshop on the management of risky alcohol use based on health advice; participants will also complete the pre-and post-workshop questionnaires and be videotaped. Study population: Patients ≥ 14 years old with risky alcohol consumption (28 Standard Drink Units-SDU-/week in men and 17 SDU/week in women) or excessive alcohol use (≥ 6 SDU in men or ≥ 4 SDU in women, in less than 2 h). It would be necessary to include 110 subjects/group to find a difference of 20% between the percentage of patients in abstinence between EG (37%) and CG (20%), alpha error of 5%, and statistical power of 80%. Assuming a loss rate of 5% and the cluster design effect, the number of subjects to be recruited is estimated at 197/group. The follow-up period will be 12 months. The primary outcome variables will be the self-reported alcohol use level and the Alcohol Use Disorders Identification Test (AUDIT) questionnaire score. Discussion: The study aims to demonstrate the effectiveness of the motivational approach in the comprehensive treatment of the patient with risky alcohol use, improving the empathy of the healthcare professionals and strengthening the healthcare professional-patient relationship to achieve the behavioral change of the patients with this problem in primary care consultations. Clinical trial registration: ClinicalTrials.gov.

Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection.

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Knowledge, attitudes and preventive practices of primary health care professionals towards alcohol use: A national, cross-sectional study.

INTRODUCTION: Primary care (PC) professionals' knowledge about alcohol use has been identified as one of the barriers PC providers face in their clinic. Both PC professionals' level of training and attitude are crucial in the clinical practice regarding alcohol use. OBJECTIVE: To evaluate the knowledge, attitude, and preventive practices of Spanish PC physicians and nurses towards alcohol use. DESIGN: An observational, descriptive, cross-sectional, multi-center study. METHODOLOGY: Location: PC centers of the Spanish National Health System (NHS). Participants: PC physicians and nurses selected randomly from health care centers, and by sending an e-mail to semFYC and SEMERGEN members. Healthcare providers completed an online survey on knowledge, attitude, and follow-up recommendations for reducing alcohol intake. A descriptive, bivariate, and multivariate statistical analysis was conducted (p<0.05). RESULTS: Participants: 1,760 healthcare providers completed the survey (75.6% [95% CI 73.5-77.6] family physicians; 11.4% [95% CI 9.9-12.9] medical residents; and 12.5% [95% CI 10.9-14.1] nurses), with a mean age of 44.7 (SD 11.24, range: 26-64, 95% CI: 47.2-48.2). Knowledge was higher in family physicians (p<0.001), older professionals (Spearman's r = 0.11, p<0.001), and resident trainers (p<0.001). The PC professional most likely to provide advice for reducing alcohol use was: a nurse (p <0.001), female (p = 0.010), between 46 and 55 years old (p <0.001). CONCLUSIONS: PC providers' knowledge and preventive practices regarding alcohol use are scarce, hence specific training strategies to increase their knowledge and improve their attitude and skills with regard to this health problem should be considered a healthcare policy priority.

Assessment of pharmacists' views on biosimilar naming conventions.

BACKGROUND: As the date for the introduction of biosimilars in the United States approaches, questions remain regarding the naming, coding, and approval process for these agents that will need to be carefully considered. OBJECTIVES: To (a) ascertain pharmacists' awareness of and comfort level with biosimilars and (b) determine the impact of identical or different nonproprietary names on pharmacists' confidence in substituting interchangeable biologics. METHODS: The Academy of Managed Care Pharmacy, the American Pharmacists Association, and the American Society of Health-System Pharmacists fielded a survey to their membership or a partial segment of their membership. The survey consisted of 2 sections: (1) current processes for reporting biologics being dispensed and (2) familiarity and preferences regarding biosimilars. RESULTS: A substantial majority (70.1%) of respondents reported regularly using National Drug Code numbers as the identifier for biological products dispensed to patients; however, 10.4% of respondents reported using either the nonproprietary name or the Healthcare Common Procedure Coding System code as the identifier. When presented with 3 scenarios for naming conventions of interchangeable biosimilars and asked to rate their level of confidence (1 = not confident, 5 = very confident) to substitute, 74.6% of pharmacists indicated that they would be confident or very confident in substituting an interchangeable biosimilar with the reference product if both shared the same active ingredient or nonproprietary name of the reference biologic; 25.3% of pharmacists were confident in substituting when the nonproprietary name is not shared with the biologic; and 37.3% of pharmacists expressed confidence in substituting when the biologic and biosimilar product did not share the same nonproprietary name because of a prefix or suffix. CONCLUSIONS: The imminent entry of biosimilars into the U.S. market highlights the need to carefully evaluate current processes of identification, reporting, and recording of the biological products dispensed. The results of this survey indicate that the ultimate decision on the naming convention for biosimilars may influence dispensing pharmacists, with the majority of respondents being most comfortable with biosimilars having the same nonproprietary name as the reference biologic.

Quality improvement initiatives: the missed opportunity for health plans.

BACKGROUND: The increase in healthcare cost without direct improvements in health outcomes, coupled with a desire to expand access to the large uninsured population, has underscored the importance of quality initiatives and organizations that provide more affordable healthcare by maximizing value. OBJECTIVES: To determine the knowledge of managed care organizations about quality organizations and initiatives and to identify potential opportunities in which pharmaceutical companies could collaborate with health plans in the development and implementation of quality initiatives. METHODS: We conducted a survey of 36 pharmacy directors and 15 medical directors of different plans during a Managed Care Network meeting in 2008. The represented plans cover almost 74 million lives in commercial, Medicare, and Medicaid programs, or a combination of them. RESULTS: The responses show limited knowledge among pharmacy and medical directors about current quality organizations and initiatives, except for quality organizations that provide health plan quality accreditation. The results also reveal an opportunity for pharmaceutical companies to collaborate with private health plans in the development of quality initiatives, especially those related to drug utilization, such as patient adherence and education and correct drug utilization. CONCLUSION: Our survey shows clearly that today's focus for managed care organizations is mostly limited to the organizations that provide health plan quality accreditation, with less focus on other organizations.

Guanine-rich DNA nanocircles for the synthesis and characterization of long cytosine-rich telomeric DNAs.

Short synthetic oligonucleotides derived from the human telomeric repeat have been studied recently for their ability to fold into four-stranded structures that are thought to be important to their biological function. Because telomeric DNAs are several kilobases in length, however, their folding might well be affected by cooperative or high-order interactions in these long sequences. Here, we present a new molecular system that allows for easy synthesis of very long stretches of the cytosine-rich strand of human telomeric DNA. Small circular DNAs composed of the G-rich sequence of human telomeres were prepared and used as templates in a rolling-circle replication mechanism. To facilitate the synthesis of the repetitive G-rich circles, an orthogonal base-protection strategy that made use of dimethylformamidine-protected guanine nucleobases was developed. Nanometer-scale circles ranging in size from 42 to 54 nucleotides were prepared. Subsequently, we tested the action of various DNA polymerases on these circular templates, and identified DNA Pol I (Klenow fragment) and T7 DNA polymerase as enzymes that are able to generate very long, C-rich telomeric DNA strands. Purification and initial structural examination of these C-rich polymeric products revealed evidence of a folded structure in the polymer.