Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Hysterectomy Trends and Risk of Vaginal Cuff Dehiscence: An Update by Mode of Surgery.

STUDY OBJECTIVE: To analyze hysterectomy trends and vaginal cuff dehiscence (VCD) rates by mode of surgery at a tertiary care medical center and to describe characteristics of VCD cases. DESIGN: Observational retrospective cohort study. SETTING: Large academic hospital and affiliated community hospital. PATIENTS: 4722 patients who underwent hysterectomy at Columbia University Irving Medical Center between January 2010 and August 2021. INTERVENTIONS: Current Procedural Terminology and International Classification of Diseases codes identified hysterectomies and VCD cases. Hysterectomy trends and VCD rates were calculated by mode of surgery. Relative risks of VCD for each mode were compared with total abdominal hysterectomy (TAH). Clinical characteristics of VCDs were reviewed. MEASUREMENTS AND MAIN RESULTS: There were 4059 total hysterectomies. Laparoscopic hysterectomies, including total laparoscopic hysterectomies (TLHs), laparoscopic-assisted vaginal hysterectomies, and robot-assisted TLHs (RA-TLHs), increased from 41.9% in 2010 to 65.9% in 2021 (p <.001). RA-TLH increased from 5.7% in 2010 to 40.2% in 2021. Supracervical hysterectomies followed similar trends and were excluded from VCD analysis. There were 15 VCDs (overall rate 0.37%). VCD was highest after RA-TLH (0.66%), followed by TLH (0.32%) and TAH (0.27%), with no VCDs after laparoscopic-assisted vaginal hysterectomy or total vaginal hysterectomy. Compared with TAH, the relative risk for VCD after RA-TLH was 2.44 (95% confidence interval 0.66-9.00) and after TLH was 1.18 (95% confidence interval 0.24-5.83), which were not statistically significant. The mean time to dehiscence was 39 days (range 8-145 days). The most common trigger event was coitus (41%). CONCLUSION: VCD rates were low (<1%) for all modes of hysterectomy, and rates after robotic and laparoscopic hysterectomy were much lower than previously reported. Although VCD rates trended higher after robotic and laparoscopic hysterectomy compared with abdominal hysterectomy, the difference was not significant. It is difficult to determine whether this finding represents true lack of difference vs a lack of power to detect a significant difference given the rarity of VCD.

Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Prevalence of LUTS and urodynamics results in obese women.

INTRODUCTION: Obesity is a well-known risk factor for lower urinary tract disorders. Lifestyle plays an essential role in the etiology of the symptoms, negatively affecting self-esteem and quality of social, professional, and sexual life. OBJECTIVES: To assess the prevalence of lower urinary tract symptoms and urodynamic patterns in obese women and to compare to nonobese volunteers. METHODS: Overactive bladder (OAB) questionaries (International Consultation on Incontinence Questionnaire [ICIQ]-OAB) and stress urinary incontinence (SUI) (ICIQ-short form) were applied to the participants. They underwent a physical exam and urodynamics except for the control group. RESULTS: A total of 109 women completed the protocol and 20 were in the control group. The average age was 43.0 years, and the average body mass index was 45.12 ± 7.64 kg/m2 and control was 44.5 years, and 29.95 ± 5.08 kg/m2 . The OAB symptoms in the obese group were 31.20%, 55.95% higher than the control group (20.0%). The prevalence of SUI in the obese group was 20.20%, an increase of 34.53% compared with the control group (15.00%). The urodynamic study (UDS) showed that the morbidly obese women have a first sensation earlier than the obese or severely obese, as well as the first desire to void. The Valsalva leak point pressure of morbidly obese women was significantly higher than the others. CONCLUSION: Among obese women, either the prevalence of SUI or OAB is significantly higher than the nonobese female population. Regarding UDS, the pattern is similar to the clinic diagnostic. The grade of obesity is directly associated with an impairment of the patient's cystometric capacity.

Hearing outcome after tympanoplasty type III.

PURPOSE: We assessed overall hearing outcome after tympanoplasty type III in chronically infected ears with cholesteatoma (CH) and without cholesteatoma: otitis media chronica mesotympanalis, tympanosclerosis, and adhesive process (COM_T_AP). METHODS: 303 surgeries were evaluated: 229 CH-group and 74 COM_T_AP-group. Air-bone gaps (PTA-ABG) with pure-tone averages (PTA-4) at four frequencies (0.5, 1, 2 and 4 kHz) were compared preoperatively, early postoperatively (< 40 days) and late postoperatively (40-400 days). Hearing outcome was compared in various types of middle-ear reconstruction and in smokers and non-smokers. Correlations between hearing outcome and predictive staging indices were evaluated: Middle Ear Risk-Index (MER-I) and Ossiculoplasty Outcome Parameter Staging-Index (OOPS-I). RESULTS: Mean PTA-ABG in the CH-group increased from 20.9 ± 11.3 dB to 22.3 ± 10.4 dB early postoperatively and decreased significantly to 19.2 ± 10.1 dB late postoperatively. Mean PTA-ABG in the COM_T_AP-group decreased significantly from 27.3 ± 10.9 dB to 20.6 ± 10.9 dB early postoperatively and decreased to 20.0 ± 12.2 dB late postoperatively. No significant difference was seen between PTA-ABG-closures of partial or total ossicular replacement prosthesis (PORP/TORP) and cartilage ossiculoplasty in the CH-group. Patients receiving TORP showed a significantly higher preoperative PTA-ABG. All reconstruction types exhibited postoperative PTA-ABG around 20 dB. In the COM_T_AP-group, smokers had a significantly higher mean PTA-ABG early postoperatively; this equalized with that of non-smokers late postoperatively. PTA-ABG-closures and MER-I or OOPS-I were not significantly correlated. CONCLUSION: Tympanoplasty type III maintains hearing in patients with cholesteatoma and significantly improves hearing in chronically inflamed ears without cholesteatoma. All investigated ossicular replacement prostheses are equally beneficial. Healing postoperatively takes longer in smokers, but they eventually catch up with non-smokers.

Perioperative Morbidity and Mortality of Patients With COVID-19 Who Undergo Urgent and Emergent Surgical Procedures.

OBJECTIVE: To evaluate the perioperative morbidity and mortality of patients with COVID-19 who undergo urgent and emergent surgery. SUMMARY BACKGROUND DATA: Although COVID-19 infection is usually associated with mild disease, it can lead to severe respiratory complications. Little is known about the perioperative outcomes of patients with COVID-19. METHODS: We examined patients who underwent urgent and emergent surgery at 2 hospitals in New York City from March 17 to April 15, 2020. Elective surgical procedures were cancelled throughout and routine, laboratory based COVID-19 screening was instituted on April 1. Mortality, complications, and admission to the intensive care unit were compared between patients with COVID-19 detected perioperatively and controls. RESULTS: Among 468 subjects, 36 (7.7%) had confirmed COVID-19. Among those with COVID-19, 55.6% were detected preoperatively and 44.4% postoperatively. Before the routine preoperative COVID-19 laboratory screening, 7.7% of cases were diagnosed preoperatively compared to 65.2% after institution of screening (P = 0.0008). The perioperative mortality rate was 16.7% in those with COVID-19 compared to 1.4% in COVID-19 negative subjects [aRR = 9.29; 95% confidence interval (CI), 5.68-15.21]. Serious complications were identified in 58.3% of COVID-19 subjects versus 6.0% of controls (aRR = 7.02; 95%CI, 4.96-9.92). Cardiac arrest, sepsis/shock, respiratory failure, pneumonia, acute respiratory distress syndrome, and acute kidney injury were more common in those with COVID-19. The intensive care unit admission rate was 36.1% in those with COVID-19 compared to 16.4% of controls (aRR = 1.34; 95%CI, 0.86-2.09). CONCLUSIONS: COVID-19 is associated with an increased risk for serious perioperative morbidity and mortality. A substantial number of patients with COVID-19 are not identified until after surgery.

Discontinuity of psychiatric care for patients with schizophrenia, relation to previous psychiatric care and practice variation between providers: a retrospective longitudinal cohort study.

BACKGROUND: Patients with schizophrenia need continuous integrated healthcare, but many discontinue their treatment, often experiencing adverse outcomes. The first objective of this study is to assess whether patient characteristics or treatment history are associated with discontinuity of psychiatric elective care. The second objective is to assess whether practice variation between providers of psychiatric care contributes to discontinuity of elective care. METHODS: A large registry-based retrospective cohort of 9194 schizophrenia patients, who were included if they received elective psychiatric care in December 2014-January 2015. Logistic regression models were used to identify predictive factors of discontinuity of care. The dependent variable was the binary variable discontinuity of care in 2016. Potential independent predictive variables were: age, sex, urbanization, and treatment history in 2013-2014. Practice variation between providers was assessed, adjusting for the case mix of patients regarding their demographic and care utilization characteristics. RESULTS: 12.9% of the patients showed discontinuity of elective psychiatric care in the follow-up year 2016. The risk of discontinuity of care in 2016 was higher in younger patients (between age 18 and 26), patients with a history of receiving less elective psychiatric care, more acute psychiatric care, more quarters with elective psychiatric care without antipsychotic medication, or receiving no elective treatment at all. No evidence for practice variation between providers was found. CONCLUSIONS: Our findings show that the pattern of previous care consumption is an important prognostic factor of future discontinuity of elective care. We propose that previous care consumption can be used to design strategies to improve treatment retention and focus resources on those most at risk of dropping out.

Where Have All the Emergencies Gone? The Impact of the COVID-19 Pandemic on Obstetric and Gynecologic Procedures and Consults at a New York City Hospital.

STUDY OBJECTIVE: The purpose of this study was to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on surgical volume and emergency department (ED) consults across obstetrics-gynecology (OB-GYN) services at a New York City hospital. DESIGN: Retrospective cohort study. SETTING: Tertiary care academic medical center in New York City. PATIENTS: Women undergoing OB-GYN ED consults or surgeries between February 1, 2020 and April 15, 2020. INTERVENTIONS: March 16 institutional moratorium on elective surgeries. MEASUREMENTS AND MAIN RESULTS: The volume and types of surgeries and ED consults were compared before and after the COVID-19 moratorium. During the pandemic, the average weekly volume of ED consults and gynecology (GYN) surgeries decreased, whereas obstetric (OB) surgeries remained stable. The proportions of OB-GYN ED consults, GYN surgeries, and OB surgeries relative to all ED consults, all surgeries, and all labor and delivery patients were 1.87%, 13.8%, 54.6% in the pre-COVID-19 time frame (February 1-March 15) vs 1.53%, 21.3%, 79.7% in the COVID-19 time frame (March 16-April 15), representing no significant difference in proportions of OB-GYN ED consults (p = .464) and GYN surgeries (p = .310) before and during COVID-19, with a proportionate increase in OB surgeries (p <.002). The distribution of GYN surgical case types changed significantly during the pandemic with higher proportions of emergent surgeries for ectopic pregnancies, miscarriages, and concern for cancer (p <.001). Alternatively, the OB surgery distribution of case types remained relatively constant. CONCLUSION: This study highlights how the pandemic has affected the ways that patients in OB-GYN access and receive care. Institutional policies suspending elective surgeries during the pandemic decreased GYN surgical volume and affected the types of cases performed. This decrease was not appreciated for OB surgical volume, reflecting the nonelective and time-sensitive nature of obstetric care. A decrease in ED consults was noted during the pandemic begging the question "Where have all the emergencies gone?" Although the moratorium on elective procedures was necessary, "elective" GYN surgeries remain medically indicated to address symptoms such as pain and bleeding and to prevent serious medical sequelae such as severe anemia requiring transfusion. As we continue to battle COVID-19, we must not lose sight of those patients whose care has been deferred.

The safety of paediatric surgery between COVID-19 surges: an observational study.

Despite the ongoing coronavirus disease 2019 (COVID-19) pandemic, elective paediatric surgery must continue safely through the first, second and subsequent waves of disease. This study presents outcome data from a children's hospital in north-west England, the region with the highest prevalence of COVID-19 in England. Children and young people undergoing elective surgery isolated within their household for 14 days, then presented for real-time reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) within 72 h of their procedure (or rapid testing within 24 h in high-risk cases), and completed a screening questionnaire on admission. Planned surgery resumed on 26 May 2020; in the four subsequent weeks, there were 197 patients for emergency and 501 for elective procedures. A total of 488 out of 501 (97.4%) elective admissions proceeded, representing a 2.6% COVID-19-related cancellation rate. There was no difference in the incidence of SARS-CoV-2 among children and young people who had or had not isolated for 14 days (p > 0.99). One out of 685 (0.1%) children who had surgery re-presented to the hospital with symptoms potentially consistent with SARS-CoV-2 within 14 days of surgery. Outcomes were similar to those in the same time period in 2019 for length of stay (p = 1.0); unplanned critical care admissions (p = 0.59); and 14-day hospital re-admission (p = 0.17). However, the current cohort were younger (p = 0.037); of increased complexity (p < 0.001) and underwent more complex surgery (p < 0.001). The combined use of household self-isolation, testing and screening questionnaires has allowed the re-initiation of elective paediatric surgery at high volume while maintaining pre-COVID-19 outcomes in children and young people undergoing surgery. This may provide a model for addressing the ongoing challenges posed by COVID-19, as well as future pandemics.

Essentials in Minimally Invasive Gynecology Manual Skills Pilot Validation Trial.

STUDY OBJECTIVE: To evaluate the Essentials in Minimally Invasive Gynecology (EMIG)- Fundamentals of Laparoscopic Surgery Laparoscopic Simulation System and the EMIG Hysteroscopy Simulation System for face validity and functionality in a pilot testing environment. DESIGN: A prospective controlled pilot study. SETTING: Three teaching institutions in the US Southwest. SUBJECTS: Twenty-seven residents and gynecologists, with 22 fitting who fit 1 of 4 categories of exposure to hysteroscopic and laparoscopic surgery and surgical simulation. Eleven were postgraduate year 1 and 5 postgraduate year 3, 1 was American Board of Obstetrics & Gynecology certified, and 5 were either fellows in-training or had completed a fellowship in minimally invasive gynecologic surgery. INTERVENTIONS: After completing a screening survey, each subject was exposed to a structured orientation to the 2 simulation systems and then tested with proctor supervision on the 5 laparoscopic and 2 hysteroscopic exercises. A short 5-point Likert questionnaire designed to determine face validation and question clarity was administered to each subject at sites 2 and 3. MEASUREMENTS AND MAIN RESULTS: Face validity was high for each of the 7 exercises (means ranged from 4.8 to 4.9 of 5), and subjects considered instructions to be clear (means from 4.7 to 4.9). The recorded exercise times generally reduced with increasing levels of training, although the sample sizes were not designed to determine significance given the pilot design. Similarly, exercise errors were generally less frequent with increasing experience. The systems, including the devices and recording mechanisms, performed well, and proctor evaluation and training were satisfactory. CONCLUSION: The EMIG laparoscopic and hysteroscopic simulations systems were considered to have good face validity and appear to be suitable for a construct validation trial to confirm their utility in distinguishing among trainees and practitioners with a wide spectrum of endoscopic surgical experience. The recording and specimen storage mechanisms will allow for multiple proctors to rate a candidate's performance, thereby enhancing evaluation consistency and quality.

Optimizing surgical management of patients who decline blood transfusion.

PURPOSE OF REVIEW: This review highlights the complexity of caring for gynecologic patients who refuse blood transfusion and discusses the importance of early, targeted perioperative and intraoperative medical optimization. We review alternative interventions and the importance of medical management to minimize blood loss and maximize hematopoiesis, particularly in gynecologic patients who may have significant uterine bleeding. The review also focuses on intraoperative interventions and surgical techniques to prevent and control surgical blood loss. RECENT FINDINGS: With improvements in surgical technique, greater availability of minimally invasive surgery, and increased use of preop UAE and cell salvage, definitive surgical management can be safely performed. New technologies have been developed that allow for safer surgeries or alternatives to traditional surgical procedures. Many medical therapies have been shown to decrease blood loss and improve surgical outcomes. Nonsurgical interventions have also been developed for use as adjuncts or alternatives to surgery. SUMMARY: The care of a patient who declines blood transfusion may be complex, but gynecologic surgeons can safely and successfully offer a wide variety of therapies depending on the patient's goals and needs. Medical management should be implemented early. A multidisciplinary team should be mobilized to provide comprehensive and patient-centered care.

Sacrospinous hysteropexy with a low weight transvaginal polypropylene mesh for treatment of complete uterovaginal eversion.

INTRODUCTION: Pelvic Organ Prolapse (POP) is a common condition in elderly resulting from the weakening of the organ suspension elements of multifactorial origin. It compromises significantly the quality of life and can affect more than 50% of multiparous women. Stage IV prolapse or complete uterovaginal eversion corresponds to 10% of the cases and the only form of curative treatment is the surgical correction. The aim of this video is to demonstrate our technique of sacrospinous hysteropexy with a low weight transvaginal polypropylene mesh for treatment of this challenge condition, focusing on technical details in order to prevent mesh related complications. Major, but rare complications, include: infection, prolapse recurrence, abscess formation, bladder perforation and urinary fistula. These situations are related mostly to low volume centers. MATERIALS AND METHODS: A 70 years old female with a stage IV POP had obstructive lower urinary tract symptoms. Only after reducing prolapse, it was possible to urinate, but without stress urinary incontinence. No topic estrogen was prescribed before the surgery and she also didn´t take any kind of hormone replacement therapy. Transvaginal ultrasound and the Pap smear screening were done with normal results. Cystoscopy wasn´t employed at anytime of this procedure. Hydrodissection of vaginal wall was followed by longitudinal incision from the level of bladder neck to the cervix. Notice that the ideal dissection should maintain the vaginal thickness, and address the plane of the connective tissue between the bladder and the vagina. Bladder base is then released from the anterior aspect of the cervix in order to create a site to pericervical ring repair and to fix the apex of the Calistar Soft® with polypropylene 3.0 stitches. A blunt dissection extended downwards through the lateral aspect of the levator ani fascia till the identification of the ischial spine and sacrospinous ligaments bilaterally. Two polypropilene 2.0 threads mounted on a specially designed tissue anchor system (TAS) are then fixed into each sacrospinous ligament 1.5 to 2 cm away from the ischial spine and repaired for further prosthesis anchoring. Then, a longitudinal incision is done at the posterior vaginal wall and the recto-vaginal fascia detachment from the posterior aspect of the pericervical ring is identified and corrected with interrupted polypropylene 2.0 stitches to the cervix and to the pericervical aspect of elongated uterosacrus ligaments bilaterally. The Calistar Soft A (anterior) and P (posterior)® prosthesis were fixed at the anterior and posterior aspects of the cervix, respectively, with interrupted polypropylene 3.0 stitches and meshes' arms are fixed to the sacrospinous ligament using the previously implanted TAS. Then, the distal Calistar Soft A® arms were bilaterally fixed into the internal obturator muscles using its fish spine-like multipoint fix device in order to prevent mesh folding. Finally, perineal body repair was done and vaginal wall was closed with individual absorbable interrupted polyglactin 2.0 sutures and a 16 Fr Foley catheter as well as a vaginal pack embedded on neomicin-bacitracin cream were kept overnight. RESULTS: A high satisfaction rate has been computed with synthetic mesh to POP surgery correction. Approximately 10% of cases of mesh exposure may occur, most of them oligosymptomatic and easy handed by excision or with topic estrogen preparations. After 1 year follow-up, our patient is still satisfied without any complain and no relapse. CONCLUSION: We described a successful treatment of stage IV POP in an old female patient. This technique can be used for advanced end stage POP patients, especially those with some contraindication to sacropromontopexy, but who want to keep vaginal length and uterus. Anatomical knowledge, obedience to technical care, and intensive training are the keys for minimizing the risk of complications. Although we had success with this technique, more studies with proper randomization are necessary to compare success and complications of sacrospinous hysteropexy with a low weight transvaginal polypropylene mesh to sacropromontopexy.

Spiro-1-benzofuranpiperidinylalkanoic acids as a novel and selective sphingosine S1P5 receptor agonist chemotype.

The synthesis and SAR of a novel class of spirobenzofuranpiperidinyl-derived alkanoic acids 6-34 as sphingosine S1P5 receptor agonists are described. The target compounds generally elicit high S1P5 receptor agonistic potencies and in general are selective against both S1P1 and S1P3 receptor subtypes. The key compound 32 shows a high bioavailability of 73% and a CNS/plasma ratio of 0.8 after oral administration in rats.

Ultrasonic Perfluorohexane-Loaded Monocyte Imaging: Toward a Minimally Invasive Technique for Selective Detection of Liver Inflammation in Fatty Liver Disease.

OBJECTIVES: To investigate the utility of ultrasonic (US) perfluorohexane (PFH)-loaded monocyte imaging for detection of liver inflammation in fatty liver disease. METHODS: C57Bl6 mice were injected intraperitoneally with tumor necrosis factor α and assessed by US PFH-loaded monocyte imaging 3 hours later. Echogenic monocytes were injected intravenously, leading to a transient increase in liver tissue intensity on a US perfusion scan. The contrast wash-out time constant was hypothesized to reflect the degree of inflammation. Next, we evaluated US PFH-loaded monocyte imaging in Ldlr-/- mice fed a 1-week high-fat/high-cholesterol diet as model for early developing nonalcoholic steatohepatitis. Adjunct analyses included tissue markers of liver inflammation. RESULTS: Tumor necrosis factor α-injected mice showed a reduced wash-out time constant (mean ± SEM, 0.013 ± 0.003; n = 8) compared to controls (0.054 ± 0.009; n = 7; P = .0006), indicative of increased inflammatory adhesion molecule expression on the endothelium. The Ldlr-/- mice fed the high-fat/high-cholesterol diet showed liver inflammation, as reflected by increased (3- to 4-fold) infiltration of inflammatory cells and increased (3- to 4-fold) gene expression of tumor necrosis factor α, integrin αM, intracellular adhesion molecule, and vascular cell adhesion molecule. However, in these mice, no difference was detected in the wash-out time constant as assessed by US PFH-loaded monocyte imaging (high-fat/high-cholesterol, 0.050 ± 0.017; n = 5; chow, 0.048 ± 0.006; n = 6; P = .91). CONCLUSIONS: Our results indicate that US PFH-loaded monocyte imaging is able to detect vascularly expressed inflammatory adhesion molecules in the mouse liver on direct endothelial stimulation. However, in our mouse model of early developing nonalcoholic steatohepatitis, we did not detect inflammation by this method, which may suggest that the time-dependent relationship between parenchymal and endothelial inflammation remains a fundamental issue to be addressed.

High Spatial Inhomogeneity in the Intima-Media Thickness of the Common Carotid Artery is Associated with a Larger Degree of Stenosis in the Internal Carotid Artery: The PARISK Study.

Purpose Inhomogeneity of arterial wall thickness may be indicative of distal plaques. This study investigates the intra-subject association between relative spatial intima-media thickness (IMT) inhomogeneity of the common carotid artery (CCA) and the degree of stenosis of plaques in the internal carotid artery (ICA). Materials and Methods We included 240 patients with a recent ischemic stroke or transient ischemic attack and mild-to-moderate stenosis in the ipsilateral ICA. IMT inhomogeneity was extracted from B-mode ultrasound recordings. The degree of ICA stenosis was assessed on CT angiography according to the European Carotid Surgery Trial method. Patients were divided into groups with a low (≤ 2 %) and a high (> 2 %) IMT inhomogeneity scaled with respect to the local end-diastolic diameter. Results 182 patients had suitable CT and ultrasound measurements. Relative CCA-IMT inhomogeneity was similar for the symptomatic and asymptomatic side (difference: 0.02 %, p = 0.85). High relative IMT inhomogeneity was associated with a larger IMT (difference: 235 µm, p < 0.001) and larger degree of ICA stenosis (difference: 5 %, p = 0.023) which remained significant (p = 0.016) after adjustment for common risk factors. Conclusion Regardless of common risk factors, high relative CCA-IMT inhomogeneity is associated with a greater degree of ICA stenosis and is therefore indicative of atherosclerotic disease. The predictive value of CCA-IMT inhomogeneity for plaque progression and recurrence of cerebrovascular symptoms will be determined in the follow-up phase of PARISK.

Optimization of N'-(arylsulfonyl)pyrazoline-1-carboxamidines by exploiting a novel interaction site in the 5-HT6 antagonistic binding pocket.

The discovery of non-basic N'-(arylsulfonyl)pyrazoline-1-carboxamidines as 5-HT6 antagonists with unique structural features was recently disclosed. Here we describe how this structural class was further developed by addressing an unexplored interaction site of the 5-HT6 receptor. Compound 13 resulting from this effort is a highly potent and selective 5-HT6 antagonist with improved metabolic stability. It is furthermore devoid of hERG affinity. Despite its modest CNS/plasma ratio, a high brain free fraction ensured substantial exposure to allow for rodent cognition studies.

AAGBI guidelines: the use of blood components and their alternatives 2016.

Blood transfusion can be life-saving. Anaesthetists regularly request and administer blood components to their patients. All anaesthetists must be familiar with indications and appropriate use of blood and blood components and their alternatives, but close liaison with haematology specialists and their local blood sciences laboratory is encouraged. Considerable changes in approaches to optimal use of blood components, together with the use of alternative products, have become apparent over the past decade, leading to a need to update previous guidelines and adapt them for the use of anaesthetists working throughout the hospital system.

How does an integrated primary care approach for patients in deprived neighbourhoods impact utilization patterns? An explorative study.

BACKGROUND: To explore changes in utilization patterns for general practice (GP) and hospital care of people living in deprived neighbourhoods when primary care providers work in a more coherent and coordinated manner by applying an integrated approach. METHODS: We compared expected (based on consumption patterns of a health insurers' total population) and actual utilization patterns in a deprived Dutch intervention district in the city of Utrecht (Overvecht) with control districts 1 (Noordwest) and 2 (Kanaleneiland) over the period 2006-2011, when an integrated care approach was increasingly provided in the intervention district. Standardized insurance claims data were used to indicate use of GP care and hospital care. RESULTS: Our findings revealed that the utilization of total GP care increased more in the intervention district than in the control districts. And that the intervention district showed a more pronounced decreasing trend in total hospital use as compared to what was expected, in particular from 2008 onwards. In addition, we observed a change in type of GP care use in the intervention district in particular: the number of regular consultations, long consultations, GP home visits and evening, night and weekend consultations were increasingly higher than expected. The intervention district also showed the largest decrease between actual and expected use of ambulatory care, clinical care and 1-day hospitalizations. CONCLUSIONS: Utilization patterns for general practice and hospital care of people living in deprived districts may change when primary care professionals work in a more coherent and coordinated manner by applying a more 'comprehensive' integrated care approach. Results support the expectation that a comprehensive integrated care approach might eventually contribute to the future sustainability of healthcare systems.