Innovations in blood pressure measurement and reporting technology: International Society of Hypertension position paper endorsed by the World Hypertension League, European Society of Hypertension, Asian Pacific Society of Hypertension, and Latin American Society of Hypertension.

Blood pressure (BP) is a key contributor to the lifetime risk of preclinical organ damage and cardiovascular disease. Traditional clinic-based BP readings are typically measured infrequently and under standardized/resting conditions and therefore do not capture BP values during normal everyday activity. Therefore, current hypertension guidelines emphasize the importance of incorporating out-of-office BP measurement into strategies for hypertension diagnosis and management. However, conventional home and ambulatory BP monitoring devices use the upper-arm cuff oscillometric method and only provide intermittent BP readings under static conditions or in a limited number of situations. New innovations include technologies for BP estimation based on processing of sensor signals supported by artificial intelligence tools, technologies for remote monitoring, reporting and storage of BP data, and technologies for BP data interpretation and patient interaction designed to improve hypertension management ("digital therapeutics"). The number and volume of data relating to new devices/technologies is increasing rapidly and will continue to grow. This International Society of Hypertension position paper describes the new devices/technologies, presents evidence relating to new BP measurement techniques and related indices, highlights standard for the validation of new devices/technologies, discusses the reliability and utility of novel BP monitoring devices, the association of these metrics with clinical outcomes, and the use of digital therapeutics. It also highlights the challenges and evidence gaps that need to be overcome before these new technologies can be considered as a user-friendly and accurate source of novel BP data to inform clinical hypertension management strategies.

Updates on the use of neuromodulation in geriatric patients.

PURPOSE OF REVIEW: In light of the updated AUA/SUFU guidelines on the diagnosis and treatment of overactive bladder (OAB), increased utilization of advanced therapies is expected in the coming years. The primary aim of this review is to summarize existing outcome and safety data on the use of neuromodulation in geriatric patients, as well as highlight recent advances in neuromodulation that may be particularly advantageous in the geriatric population. RECENT FINDINGS: There are mixed data demonstrating efficacy of sacral neuromodulation by decade of life, with older individuals most often demonstrating lower odds of progressing to stage 2 implantation. However, a large majority of patients still undergo stage 2 implantation with no significant increase in complications reported when compared to younger cohorts. Neuromodulation is broadening to have wider indications outside of OAB, which may be particularly beneficial in the elderly population (fecal incontinence, nonobstructive urinary retention, and constipation). Posterior tibial nerve stimulation remains a well tolerated and efficacious treatment for OAB, with new FDA-approved implantable devices joining the commercial market, which may expand access for elderly populations. SUMMARY: The data are encouraging and support the use of neuromodulation in geriatric patients.

The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy - the TABANETOC trial: study protocol for a randomized clinical multicenter trial.

BACKGROUND: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. PURPOSE: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. MATERIAL AND METHODS: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. PATIENTS: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0-1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. INTERPRETATION: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.

P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy.

BACKGROUND: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques. METHODS: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques. RESULTS: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4-61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40-1.98, P  < 0.001] and hsCRP [OR 2.25, (95% CI 1.89-2.60), P  < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72-3.10), P  < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05-1.38), P  = 0.007. CONCLUSION: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.

Informing the surgical workforce pathway: how rural community characteristics matter.

INTRODUCTION: Rural areas worldwide face a general surgeon shortage, limiting rural populations' access to surgical care. While individual and practice-related factors have been well-studied in the US, we need a better understanding of the role of community characteristics in surgeons' location choices. This study aimed to understand the deeper meanings surgeons associated with community characteristics in order to inform efforts spanning the rural surgeon workforce pathway, from early educational exposures, and undergraduate and graduate medical education, to recruitment and retention. METHODS: We conducted a qualitative, descriptive interview study with general surgeons in the Midwestern US about the role and meaning of community characteristics, exploring their backgrounds, education, practice location choices, and future plans. We focused on rural surgeons and used an urban comparison group. We used convenience and snowball sampling, then conducted interviews in-person and via phone, and digitally recorded and professionally transcribed them. We coded inductively and continued collecting data until reaching code saturation. We used thematic network analysis to organize codes and draw conclusions. RESULTS: A total of 37 general surgeons (22 rural and 15 urban) participated. Interviews totaled over 52 hours. Three global themes described how rural surgeons associated different, often deeper, meanings with certain community characteristics compared to their urban colleagues: physical environment symbolism, health resources' relationship to scope of practice, and implications of intense role overlap (professional and personal roles). All interviewees spoke to all three themes, but the meanings they found differed importantly between urban and rural surgeons. Physical landscapes and community infrastructure were representative of autonomy and freedom for rural surgeons. They also shared how facilities, equipment, staff, staff education, and surgical partners combined to create different scopes of practice than their urban counterparts experienced. Often, rural surgeons found these resources dictated when they needed to transfer patients to higher-acuity facilities. Rural surgeons experienced role overlap intensely, as they cared for patients who were also friends and neighbors. CONCLUSION: Rural surgeons associated different meanings with certain community characteristics than their urban counterparts. As they work with prospective rural surgeons, educators and rural communities should highlight how health resources can translate into desired scopes of practice. They also should share with trainees the realities of role overlap, both how intense and stressful it can be but also how gratifying. Educators should include the rural social context in medical and surgical education, looking for even more opportunities to collaborate with rural communities to provide learners with firsthand experiences of rural environments, resources, and role overlap.

Assessment of Nocturnal Blood Pressure: Importance of Determining the Time in Bed-A Pilot Study.

Objectives: Nocturnal blood pressure (BP) monitoring is essential for evaluating cardiovascular risk and guiding treatment decisions. However, the standardized narrow-fixed nighttime period between 10 p.m. and 6 a.m. may not accurately reflect individual sleep schedules. This pilot study aimed to investigate the comparability between the standardized nighttime period and actual time in bed (TIB) regarding BP assessment. Further, our goal was to evaluate the clinical relevance of the observed BP differences. Methods: A total of 30 participants underwent 24 h ambulatory blood pressure monitoring (ABPM). Patient-specific TIB was precisely assessed through an accelerometer and a position sensor from the SOMNOtouch NIBP™ (SOMNOmedics GmbH, Randersacker, Germany). We analysed the effect of considering individual TIB as nighttime instead of the conventional narrow-fixed interval on the resulting nocturnal BP levels and dipping patterns. Results: We observed differences in both systolic and diastolic BP between the standardized nighttime period and the TIB. Furthermore, a notable percentage of patients (27%) changed their dipping pattern classification as a function of the nighttime definition adopted. We found strong correlations between the start (r = 0.75, p < 0.01), as well as the duration (r = -0.42, p = 0.02) of TIB and the changes in dipping pattern classification. Conclusions: Definition of nocturnal period based on the individual TIB leads to clinically relevant changes of nocturnal BP and dipping pattern classifications. TIB is easily detected using a body position sensor and accelerometer. This approach may thus improve the accuracy of cardiovascular risk evaluation and enhance treatment strategies.

Optimizing Nanosuspension Drug Release and Wound Healing Using a Design of Experiments Approach: Improving the Drug Delivery Potential of NDH-4338 for Treating Chemical Burns.

NDH-4338 is a highly lipophilic prodrug comprising indomethacin and an acetylcholinesterase inhibitor. A design of experiments approach was used to synthesize, characterize, and evaluate the wound healing efficacy of optimized NDH-4338 nanosuspensions against nitrogen mustard-induced skin injury. Nanosuspensions were prepared by sonoprecipitation in the presence of a Vitamin E TPGS aqueous stabilizer solution. Critical processing parameters and material attributes were optimized to reduce particle size and determine the effect on dissolution rate and burn healing efficacy. The antisolvent/solvent ratio (A/S), dose concentration (DC), and drug/stabilizer ratio (D/S) were the critical sonoprecipitation factors that control particle size. These factors were subjected to a Box-Behnken design and response surface analysis, and model quality was assessed. Maximize desirability and simulation experiment optimization approaches were used to determine nanosuspension parameters with the smallest size and the lowest defect rate within the 10-50 nm specification limits. Optimized and unoptimized nanosuspensions were prepared and characterized. An established depilatory double-disc mouse model was used to evaluate the healing of nitrogen mustard-induced dermal injuries. Optimized nanosuspensions (A/S = 6.2, DC = 2% w/v, D/S = 2.8) achieved a particle size of 31.46 nm with a narrow size range (PDI = 0.110) and a reduced defect rate (42.2 to 6.1%). The optimized nanosuspensions were stable and re-dispersible, and they showed a ~45% increase in cumulative drug release and significant edema reduction in mice. Optimized NDH-4338 nanosuspensions were smaller with more uniform sizes that led to improved physical stability, faster dissolution, and enhanced burn healing efficacy compared to unoptimized nanosuspensions.