mental health.BACKGROUND In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed. METHODS An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS. RESULTS Phase-A enrolled 128 patients; median age was 64 years (range 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI 7.9-10.8) for Phase-A and 6.7 months (95% CI 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group. CONCLUSIONS Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR. TRIAL REGISTRATION ClinicalTrials.gov NCT01588990; posted May 1, 2012.INTRODUCTION Aggression is a clinical symptom of various psychiatric disorders that can be conceptualised as a physical act towards another person with the intent to cause harm. In antisocial personality disorder (ASPD), aggression is a frequent manifestation that differently compromise therapeutic and prognostic goals according to its impulsive or premeditated categorisation. ASPD is characterised by high levels of impulsivity, psychopathic traits, and a high prevalence of co-morbid substance use disorders (SUDs). Aggression in ASPD patients may determine long and recurrent imprisonment thus representing a challenge clinicians and legal experts face. OBJECTIVES Our aims were to characterise impulsive and premeditated aggression in male ASPD offenders as well as to determine the potential role of SUDs, impulsivity, and psychopathic traits as predictors. MATERIALS AND METHODS In this cross-sectional study we evaluated a sample of ASPD offenders with a battery of clinical and psychometric, standardised instrumeth ASPD is mainly impulsive in nature. ASPD patients who have higher scores of psychopathic traits have a lower probability of exhibiting impulsive aggression and a higher probability of exhibiting premeditated aggression. Although ASPD patients have high levels of impulsivity and a high frequency of SUDs, these two variables were not predictors of the aggression type.We tested a feminist social-ecological model to understand community influences on daughters' experience of female genital mutilation/cutting (FGMC) in Egypt, where over 90% of women ages 15-49 are cut. FGMC has potential adverse effects on demographic and health outcomes and has been defined as a human-rights violation. However, an integrated multilevel-level framework is lacking. We theorized that a more favorable community-level gender system, including stronger gender norms opposing FGMC and expanded extra-familial opportunities for women in the village or neighborhood, would be associated with a daughter's lower risk of FGMC and would strengthen the negative association of a mother's opposition to FGMC with her daughter's risk of cutting. Using a national sample of 14,171 mother-daughter dyads from the 2014 Egypt Demographic and Health Survey, we estimated multilevel discrete-time hazard models to test these relationships. Community gender norms opposing FGMC had significant direct, negative associations with the hazard that a daughter was cut, but women's opportunities outside the family did not. Maternal opposition to FGMC was negatively associated with cutting a daughter, and these associations were stronger where community opposition to FGMC and opportunities for women were greater. Results provided good support for a gender-systems framework of the multilevel influences on FGMC. Integrated, multilevel interventions that address gender norms about FGMC and structural opportunities for women in the community, as well as beliefs about the practice among the mothers of at-risk daughters, may be needed for sustainable declines in the practice.OBJECTIVES To test the feasibility of a randomized controlled study design comparing epidural analgesia (EDA) with continuous wound infiltration (CWI) in respect to postoperative complications and mobility to design a future multicentre randomized controlled trial. DESIGN, SETTING, PARTICIPANTS CWI has been developed to address drawbacks of EDA. Previous studies have established the equivalent analgesic potential of CWI compared to EDA. This is a single centre, non-blinded pilot randomized controlled trial at a tertiary surgical centre. Patients undergoing elective non-colorectal surgery via a midline laparotomy were randomized to EDA or CWI. Endpoints included recruitment, feasibility of assessing postoperative mobility with a pedometer and morbidity. No primary endpoint was defined and all analyses were explorative. https://www.selleckchem.com/products/iclepertin.html INTERVENTIONS CWI with local anaesthetics (experimental group) vs. thoracic EDA (control). RESULTS Of 846 patients screened within 14 months, 71 were randomized and 62 (31 per group) included in the intention-to-treat analysis. Mobility was assessed in 44 of 62 patients and revealed no differences within the first 3 postoperative days. Overall morbidity did not differ between the two groups (measured via the comprehensive complication index). Median pain scores at rest were comparable between the two groups, while EDA was superior in pain treatment during movement on the first, but not on the second and third postoperative day. Duration of preoperative induction of anaesthesia was shorter with CWI than with EDA. Of 17 serious adverse events, 3 were potentially related to EDA, while none was related to CWI. CONCLUSION This trial confirmed the feasibility of a randomized trial design to compare CWI and EDA regarding morbidity. Improvements in the education and training of team members are necessary to improve recruitment. TRIAL REGISTRATION DRKS00008023.
mental health.BACKGROUND In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed. METHODS An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS. RESULTS Phase-A enrolled 128 patients; median age was 64 years (range 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI 7.9-10.8) for Phase-A and 6.7 months (95% CI 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group. CONCLUSIONS Results from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR. TRIAL REGISTRATION ClinicalTrials.gov NCT01588990; posted May 1, 2012.INTRODUCTION Aggression is a clinical symptom of various psychiatric disorders that can be conceptualised as a physical act towards another person with the intent to cause harm. In antisocial personality disorder (ASPD), aggression is a frequent manifestation that differently compromise therapeutic and prognostic goals according to its impulsive or premeditated categorisation. ASPD is characterised by high levels of impulsivity, psychopathic traits, and a high prevalence of co-morbid substance use disorders (SUDs). Aggression in ASPD patients may determine long and recurrent imprisonment thus representing a challenge clinicians and legal experts face. OBJECTIVES Our aims were to characterise impulsive and premeditated aggression in male ASPD offenders as well as to determine the potential role of SUDs, impulsivity, and psychopathic traits as predictors. MATERIALS AND METHODS In this cross-sectional study we evaluated a sample of ASPD offenders with a battery of clinical and psychometric, standardised instrumeth ASPD is mainly impulsive in nature. ASPD patients who have higher scores of psychopathic traits have a lower probability of exhibiting impulsive aggression and a higher probability of exhibiting premeditated aggression. Although ASPD patients have high levels of impulsivity and a high frequency of SUDs, these two variables were not predictors of the aggression type.We tested a feminist social-ecological model to understand community influences on daughters' experience of female genital mutilation/cutting (FGMC) in Egypt, where over 90% of women ages 15-49 are cut. FGMC has potential adverse effects on demographic and health outcomes and has been defined as a human-rights violation. However, an integrated multilevel-level framework is lacking. We theorized that a more favorable community-level gender system, including stronger gender norms opposing FGMC and expanded extra-familial opportunities for women in the village or neighborhood, would be associated with a daughter's lower risk of FGMC and would strengthen the negative association of a mother's opposition to FGMC with her daughter's risk of cutting. Using a national sample of 14,171 mother-daughter dyads from the 2014 Egypt Demographic and Health Survey, we estimated multilevel discrete-time hazard models to test these relationships. Community gender norms opposing FGMC had significant direct, negative associations with the hazard that a daughter was cut, but women's opportunities outside the family did not. Maternal opposition to FGMC was negatively associated with cutting a daughter, and these associations were stronger where community opposition to FGMC and opportunities for women were greater. Results provided good support for a gender-systems framework of the multilevel influences on FGMC. Integrated, multilevel interventions that address gender norms about FGMC and structural opportunities for women in the community, as well as beliefs about the practice among the mothers of at-risk daughters, may be needed for sustainable declines in the practice.OBJECTIVES To test the feasibility of a randomized controlled study design comparing epidural analgesia (EDA) with continuous wound infiltration (CWI) in respect to postoperative complications and mobility to design a future multicentre randomized controlled trial. DESIGN, SETTING, PARTICIPANTS CWI has been developed to address drawbacks of EDA. Previous studies have established the equivalent analgesic potential of CWI compared to EDA. This is a single centre, non-blinded pilot randomized controlled trial at a tertiary surgical centre. Patients undergoing elective non-colorectal surgery via a midline laparotomy were randomized to EDA or CWI. Endpoints included recruitment, feasibility of assessing postoperative mobility with a pedometer and morbidity. No primary endpoint was defined and all analyses were explorative. https://www.selleckchem.com/products/iclepertin.html INTERVENTIONS CWI with local anaesthetics (experimental group) vs. thoracic EDA (control). RESULTS Of 846 patients screened within 14 months, 71 were randomized and 62 (31 per group) included in the intention-to-treat analysis. Mobility was assessed in 44 of 62 patients and revealed no differences within the first 3 postoperative days. Overall morbidity did not differ between the two groups (measured via the comprehensive complication index). Median pain scores at rest were comparable between the two groups, while EDA was superior in pain treatment during movement on the first, but not on the second and third postoperative day. Duration of preoperative induction of anaesthesia was shorter with CWI than with EDA. Of 17 serious adverse events, 3 were potentially related to EDA, while none was related to CWI. CONCLUSION This trial confirmed the feasibility of a randomized trial design to compare CWI and EDA regarding morbidity. Improvements in the education and training of team members are necessary to improve recruitment. TRIAL REGISTRATION DRKS00008023.
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