Insurance Firms in Process of Industrialization

Background: Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo) radiotherapy compared to primary perineal wound closure. Methods/Design: In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo) radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion: The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia

The Effect of Lattice Vibrations on Substitutional Alloy Thermodynamics

A longstanding limitation of first-principles calculations of substitutional alloy phase diagrams is the difficulty to account for lattice vibrations. A survey of the theoretical and experimental literature seeking to quantify the impact of lattice vibrations on phase stability indicates that this effect can be substantial. Typical vibrational entropy differences between phases are of the order of 0.1 to 0.2 k_B/atom, which is comparable to the typical values of configurational entropy differences in binary alloys (at most 0.693 k_B/atom). This paper describes the basic formalism underlying ab initio phase diagram calculations, along with the generalization required to account for lattice vibrations. We overview the various techniques allowing the theoretical calculation and the experimental determination of phonon dispersion curves and related thermodynamic quantities, such as vibrational entropy or free energy. A clear picture of the origin of vibrational entropy differences between phases in an alloy system is presented that goes beyond the traditional bond counting and volume change arguments. Vibrational entropy change can be attributed to the changes in chemical bond stiffness associated with the changes in bond length that take place during a phase transformation. This so-called ``bond stiffness vs. bond length'' interpretation both summarizes the key phenomenon driving vibrational entropy changes and provides a practical tool to model them.Comment: Submitted to Reviews of Modern Physics 44 pages, 6 figure

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Propensity Score Adjusted Comparison of Pelviperineal Morbidity with and Without Omentoplasty Following Abdominoperineal Resection for Primary Rectal Cancer

BACKGROUND: Abdominoperineal resection is associated with a high incidence of perineal complications, and whether this is reduced by an omentoplasty is still unclear. OBJECTIVE: This study aimed to investigate the impact of omentoplasty on pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer. DESIGN: This was a retrospective comparative cohort study using propensity score analyses to reduce potential confounding. SETTING: The study was undertaken in 2 teaching hospitals and 1 university hospital. PATIENTS: Patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The main end points were primary perineal wound healing at 30 days and overall and specific pelviperineal morbidity until the end of the study period. RESULTS: Among 254 included patients, 106 had an omentoplasty. The primary perineal wound healing rate at 30 days was similar for omentoplasty and no omentoplasty (65% vs 60%; p = 0.422), also after adjusting for potential confounding by propensity score analysis (OR, 0.89; 95% CI, 0.45-1.75). Being free from any pelviperineal complication at 6 months (75% vs 79%; p = 0.492), absence of any pelviperineal morbidity until 1 year (54% vs 49%; p = 0.484), and incidence of persistent perineal sinus (6% vs 10%; p = 0.256) were also similar in both groups. The unadjusted higher perineal hernia rate after omentoplasty (18% vs 7%; p = 0.011) did not remain statistically significant after regression analysis including the propensity score (OR, 1.34; 95% CI, 0.46-3.88). Complications related to the omentoplasty itself were observed in 8 patients, of whom 6 required reoperation. LIMITATIONS: This study was limited by the retrospective and nonrandomized design causing some heterogeneity between the 2 cohorts. CONCLUSION: In this multicenter study using propensity score analyses, the use of omentoplasty did not lower the incidence or the duration of pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer, and omentoplasty itself was associated with a risk of reoperation. See Video Abstract at http://links.lww.com/DCR/A918

General practitioners' involvement during survivorship care of colon cancer in the Netherlands: primary health care utilization during survivorship care of colon cancer, a prospective multicentre cohort study

BACKGROUND: Primary health care use increases when cancer is diagnosed. This increase continues after cancer treatment. More generalist care is suggested to improve survivorship care. It is unknown to what extent cancer-related symptoms are currently presented in primary care in this survivorship phase. OBJECTIVE: To analyse primary health care utilization of colon cancer patients during and after treatment with curative intent. METHODS: In a prospective multicentre cohort study among patients with curatively treated colon cancer, we describe the primary health care utilization during the first 5 years of follow-up. Data were collected at general practitioner (GP) practices during 6 months. RESULTS: Of 183 included participants, 153 (84%) consulted their GP resulting in 606 contacts (mean 3.3, standard deviation 3.01) with on average 0.9 contact for colon-cancer-related (CCR) problems in the 6-month study period. Median time after surgery at inclusion was 7.6 months (range 0-58). Abdominal pain and chemotherapy-related problems were the most frequently reported CCR reasons. Of the CCR contacts, 83% was managed in primary care. As time after surgery passed, the number of CCR contacts declined in patients without chemotherapy and remained constant in patients who received chemotherapy. CONCLUSION: Colon cancer survivors contact their GP frequently also for reasons related to cancer. Currently, a formal role for GPs in survivorship care is lacking, but nevertheless GPs provide a substantial amount of care. Working agreements between primary and secondary care are necessary to formalize the GP's role in order to improve the quality of survivorship care

Comparing video consultation and telephone consultation at the outpatient clinic of a tertiary referral centre: Patient and provider benefits

Objectives Telephone consultations are frequently used in the outpatient setting in order to avoid unnecessary travel and to reduce hospital visit-related costs for patients. However, they are limited by the absence of non-verbal communication in contrast to video consultation. Little is known considering the possible advantages of using video consultation in comparison to telephone consultation according to both patients and healthcare providers. Methods Patients with colorectal diseases were asked to choose between a telephone consultation or a video consultation for their next appointment at the outpatient clinic of a tertiary referral centre. Willingness to use video consultation, value of non-verbal communication, patient satisfaction, provider satisfaction and user friendliness of the video connection technology were measured using questionnaires. Results None of the included patients ever had a video consultation before with a healthcare provider. Nonetheless, 22/50 preferred a video consultation over a telephone consultation. Patients who preferred a video consultation underlined the benefits of providing visual feedback to both patients and healthcare providers. Moreover, healthcare providers felt they were better able to assess the patients' healthcare condition. Conclusion For patients who value both verbal and non-verbal interaction and feel comfortable with the use of video consultation, video consultation is the preferred contact modality. Shared decision making should be used to choose the preferred interaction modality. For patients with low digital skills, support might be needed or video consultation may not be the preferred choice