Guideline-discordant care among females undergoing groin hernia repair: the importance of sex as a biologic variable.

PURPOSE: Females suffer higher rates of operative recurrence and chronic pain following groin hernia repair. Guidelines recommend minimally invasive (MIS) groin hernia repair as the preferred approach to reduce these adverse outcomes. It is unknown what proportion of females receive MIS hernia repair. Therefore, our goal was to investigate adoption of evidence-based practices in groin hernia repair using sex as a biological variable. METHODS: Retrospective cohort study of adults undergoing elective groin hernia repair (2014-2019) within a statewide quality improvement collaborative. Primary outcome was surgical approach. Multivariable logistic regression was performed to analyze the likelihood of undergoing MIS hernia repair. Secondary outcomes were 30-day adjusted rates of clinical and patient-reported outcomes (PROs). PROs included regret to undergo surgery among patients who completed post-operative surveys. RESULTS: Among 23,723 patients, the majority (90.7%) were males. Compared to males, females less often underwent an MIS surgical approach (37.4% vs 45.1%, p < 0.0001). After adjustment for patient and clinical variables, females remained significantly less likely to undergo MIS groin hernia repair (aOR 0.88, 95% CI 0.80-0.97). Adjusted clinical outcomes were not different between males and females. Among 4325 patients who completed post-operative surveys, adjusted rates of regret to undergo surgery were higher among females (12.9% vs 8.5%, p = 0.003). CONCLUSIONS: Even after adjusting for differences, females were less likely to receive guideline-concordant groin hernia repair and were more likely to regret surgery. Understanding the behaviors of surgeons who treat females with groin hernia may inform quality metrics to promote best practices in this population.

2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity.

BACKGROUND: Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, 3 isoforms have been identified. Their allergenicity has not been elucidated. OBJECTIVE: This study investigated the allergenicity of Ara h 7 isoforms compared to Ara h 2 and 6. METHODS: Sensitization of 15 DBPCFC-confirmed peanut-allergic patients to recombinant Ara h 2.0201, Ara h 6.01 and isoforms of recombinant Ara h 7 was determined by IgE immunoblotting strips. A basophil activation test (BAT) was performed in 9 patients to determine IgE-cross-linking capacities of the allergens. Sensitivity to the allergens was tested in 5 patients who were sensitized to at least 1 Ara h 7 isoform, by a concentration range in the BAT. 3D prediction models and sequence alignments were used to visualize differences between isoforms and to predict allergenic epitope regions. RESULTS: Sensitization to Ara h 7.0201 was most frequent (80%) and showed to be equally potent as Ara h 2.0201 and 6.01 in inducing basophil degranulation. Sensitization to Ara h 7.0201 together with Ara h 2.0201 and/or 6.01 was observed, indicating the presence of unique epitopes compared to the other 2 isoforms. Differences between the 3 Ara h 7 isoforms were observed in C-terminal cysteine residues, pepsin and trypsin cleavage sites and 3 single amino acid substitutions. CONCLUSION & CLINICAL RELEVANCE: The majority of peanut-allergic patients are sensitized to isoform Ara h 7.0201, which is functionally as active as Ara h 2.0201 and 6.01. Unique epitopes are most likely located in the C-terminus or an allergenic loop region which is a known allergenic epitope region for Ara h 2.0201 and 6.01. Due to its unique epitopes and allergenicity, it is an interesting candidate to improve the diagnostic accuracy for peanut allergy.

BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes.

Patients with asthma experience circadian variations in their symptoms. However it remains unclear how specific aspects of this common airway disease relate to clock genes, which are critical to the generation of circadian rhythms in mammals. Here, we used a viral model of acute and chronic airway disease to examine how circadian clock disruption affects asthmatic lung phenotypes. Deletion of the core clock gene bmal1 or environmental disruption of circadian function by jet lag exacerbated acute viral bronchiolitis caused by Sendai virus (SeV) and influenza A virus in mice. Post-natal deletion of bmal1 was sufficient to trigger increased SeV susceptibility and correlated with impaired control of viral replication. Importantly, bmal1-/- mice developed much more extensive asthma-like airway changes post infection, including mucus production and increased airway resistance. In human airway samples from two asthma cohorts, we observed altered expression patterns of multiple clock genes. Our results suggest a role for bmal1 in the development of asthmatic airway disease via the regulation of lung antiviral responses to common viral triggers of asthma.

[Delegation of medical activities in acute pain therapy]. / Delegation ärztlicher Tätigkeiten in der Akutschmerztherapie.

Acute pain management is an interprofessional and interdisciplinary task and requires a good and trustful cooperation between stakeholders. Despite provisions in Germany according to which medical treatment can only be rendered by a formally qualified physician ("Arztvorbehalt"), a physician does not have to carry out every medical activity in person. Under certain conditions, some medical activities can be delegated to medical auxiliary personnel but they need to be (1) instructed, (2) supervised and (3) checked by the physician himself; however, medical history, diagnostic assessment and evaluation, indications, therapy planning (e.g. selection, dosage), therapeutic decisions (e. g. modification or termination of therapy) and obtaining informed consent cannot be delegated. With respect to drug therapy, monitoring of the therapy remains the personal responsibility of the physician, while the actual application of medication can be delegated. From a legal perspective, the current practice needs to be stressed about what is within the mandatory requirements and what is not when medical activities are delegated to non-medical staff. The use of standards of care improves treatment quality but like any medical treatment it must be based on the physician's individual assessment and indications for each patient and requires personal contact between physician and patient. Delegation on the ward and in acute pain therapy requires the authorization of the delegator to give instructions in the respective setting. The transfer of non-delegable duties to non-medical personnel is regarded as medical malpractice.

Cold atmospheric pressure plasma for treatment of chronic wounds: drug or medical device?

OBJECTIVE: The use of cold atmospheric pressure plasma (CAPP) as a new therapeutic option to aid the healing of chronic wounds appears promising. Currently, uncertainty exists regarding their classification as medical device or medical drug. Because the classification of CAPP has medical, legal, and economic consequences as well as implications for the level of preclinical and clinical testing, the correct classification is not an academic exercise, but an ethical need. METHOD: A multidisciplinary team of physicians, surgeons, pharmacists, physicists and lawyers has analysed the physical and technical characteristics as well as legal conditions of the biological action of CAPP. RESULTS: It was concluded that the mode of action of the locally generated CAPP, with its main active components being different radicals, is pharmacological and not physical in nature. CONCLUSION: Depending on the intended use, CAPP should be classified as a drug, which is generated by use of a medical device directly at the point of therapeutic application.

Iminophosphanes: Synthesis, Rhodium Complexes, and Ruthenium(II)-Catalyzed Hydration of Nitriles.

Highly stable iminophosphanes, obtained from alkylating nitriles and reaction of the resulting nitrilium ions with secondary phosphanes, were explored as tunable P-monodentate and 1,3-P,N bidentate ligands in rhodium complexes. X-ray crystal structures are reported for both κ1 and κ2 complexes with the counterion in one of them being an unusual anionic coordination polymer of silver triflate. The iminophosphane-based ruthenium(II)-catalyzed hydration of benzonitrile in 1,2-dimethoxyethane (180 °C, 3 h) and water (100 °C, 24 h) and under solvent free conditions (180 °C, 3 h) results in all cases in the selective formation of benzamide with yields of up to 96%, thereby outperforming by far the reactions in which the common 2-pyridyldiphenylphosphane is used as the 1,3-P,N ligand.

Virtual reality in the assessment, understanding, and treatment of mental health disorders.

Mental health problems are inseparable from the environment. With virtual reality (VR), computer-generated interactive environments, individuals can repeatedly experience their problematic situations and be taught, via evidence-based psychological treatments, how to overcome difficulties. VR is moving out of specialist laboratories. Our central aim was to describe the potential of VR in mental health, including a consideration of the first 20 years of applications. A systematic review of empirical studies was conducted. In all, 285 studies were identified, with 86 concerning assessment, 45 theory development, and 154 treatment. The main disorders researched were anxiety (n = 192), schizophrenia (n = 44), substance-related disorders (n = 22) and eating disorders (n = 18). There are pioneering early studies, but the methodological quality of studies was generally low. The gaps in meaningful applications to mental health are extensive. The most established finding is that VR exposure-based treatments can reduce anxiety disorders, but there are numerous research and treatment avenues of promise. VR was found to be a much-misused term, often applied to non-interactive and non-immersive technologies. We conclude that VR has the potential to transform the assessment, understanding and treatment of mental health problems. The treatment possibilities will only be realized if - with the user experience at the heart of design - the best immersive VR technology is combined with targeted translational interventions. The capability of VR to simulate reality could greatly increase access to psychological therapies, while treatment outcomes could be enhanced by the technology's ability to create new realities. VR may merit the level of attention given to neuroimaging.

A prospective study of pre-trauma risk factors for post-traumatic stress disorder and depression.

BACKGROUND: It is unclear which potentially modifiable risk factors best predict post-trauma psychiatric disorders. We aimed to identify pre-trauma risk factors for post-traumatic stress disorder (PTSD) or major depression (MD) that could be targeted with resilience interventions. METHOD: Newly recruited paramedics (n = 453) were assessed for history of mental disorders with structured clinical interviews within the first week of their paramedic training and completed self-report measures to assess hypothesized predictors. Participants were assessed every 4 months for 2 years to identify any episodes of PTSD and MD; 386 paramedics (85.2%) participated in the follow-up interviews. RESULTS: In all, 32 participants (8.3%) developed an episode of PTSD and 41 (10.6%) an episode of MD during follow-up. In all but nine cases (2.3%), episodes had remitted by the next assessment 4 months later. At 2 years, those with episodes of PTSD or MD during follow-up reported more days off work, poorer sleep, poorer quality of life, greater burn-out; and greater weight-gain for those with PTSD. In line with theories of PTSD and depression, analyses controlling for psychiatric and trauma history identified several pre-trauma predictors (cognitive styles, coping styles and psychological traits). Logistic regressions showed that rumination about memories of stressful events at the start of training uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD. CONCLUSIONS: Participants at risk of developing episodes of PTSD or depression could be identified within the first week of paramedic training. Cognitive predictors of episodes of PTSD and MD are promising targets for resilience interventions.

Post-traumatic stress influences the brain even in the absence of symptoms: A systematic, quantitative meta-analysis of neuroimaging studies.

Stress affects brain function, and may lead to post-traumatic stress disorder (PTSD). Considerable empirical data for the neurobiology of PTSD has been derived from neuroimaging studies, although findings have proven inconsistent. We used an activation likelihood estimation analysis to explore differences in brain activity between adults with and without PTSD in response to affective stimuli. We separated studies by type of control group: trauma-exposed and trauma-naïve. This revealed distinct patterns of differences in functional activity. Compared to trauma-exposed controls, regions of the basal ganglia were differentially active in PTSD; whereas the comparison with trauma-naïve controls revealed differential involvement in the right anterior insula, precuneus, cingulate and orbitofrontal cortices known to be involved in emotional regulation. Changes in activity in the amygdala and parahippocampal cortex distinguished PTSD from both control groups. Results suggest that trauma has a measurable, enduring effect upon the functional dynamics of the brain, even in individuals who experience trauma but do not develop PTSD. These findings contribute to the understanding of whole-brain network activity following trauma, and its transition to clinical PTSD.

Paranoia and post-traumatic stress disorder in the months after a physical assault: a longitudinal study examining shared and differential predictors.

BACKGROUND: Being physically assaulted is known to increase the risk of the occurrence of post-traumatic stress disorder (PTSD) symptoms but it may also skew judgements about the intentions of other people. The objectives of the study were to assess paranoia and PTSD after an assault and to test whether theory-derived cognitive factors predicted the persistence of these problems. METHOD: At 4 weeks after hospital attendance due to an assault, 106 people were assessed on multiple symptom measures (including virtual reality) and cognitive factors from models of paranoia and PTSD. The symptom measures were repeated 3 and 6 months later. RESULTS: Factor analysis indicated that paranoia and PTSD were distinct experiences, though positively correlated. At 4 weeks, 33% of participants met diagnostic criteria for PTSD, falling to 16% at follow-up. Of the group at the first assessment, 80% reported that since the assault they were excessively fearful of other people, which over time fell to 66%. Almost all the cognitive factors (including information-processing style during the trauma, mental defeat, qualities of unwanted memories, self-blame, negative thoughts about self, worry, safety behaviours, anomalous internal experiences and cognitive inflexibility) predicted later paranoia and PTSD, but there was little evidence of differential prediction. CONCLUSIONS: Paranoia after an assault may be common and distinguishable from PTSD but predicted by a strikingly similar range of factors.

Dose dependent molecular effects of acrylamide and glycidamide in human cancer cell lines and human primary hepatocytes.

Recently published studies suggest a weak positive correlation between increased dietary acrylamide intake and the increased risk of endometrial and ovarian cancer. However, risk assessment of acrylamide remains difficult because the carcinogenic mechanisms are still unknown and in particular the molecular effects of low level acrylamide exposure as seen by dietary intake are not well understood. Therefore, we analyzed in ovarian and endometrial cancer cell lines as well as in primary hepatocytes the expression of genes involved in cancer development and xenobiotic metabolism after high and low dose exposure (1-0.001mM) of acrylamide and its metabolite glycidamide. In conclusion our in vitro results demonstrate that exposure to high doses of glycidamide/acrylamide - exceeding the dietary exposure of the general population by far - can induce genes with growth promoting potential like the oncogene cMYC and genes involved in the MAPK pathway. However, low-dose exposure seems to activate primarily genes involved in the elimination of the toxicant.

Perceptual processing advantages for trauma-related visual cues in post-traumatic stress disorder.

BACKGROUND: Intrusive re-experiencing in post-traumatic stress disorder (PTSD) comprises distressing sensory impressions from the trauma that seem to occur 'out of the blue'. A key question is how intrusions are triggered. One possibility is that PTSD is characterized by a processing advantage for stimuli that resemble those that accompanied the trauma, which would lead to increased detection of such cues in the environment. METHOD: We used a blurred picture identification task in a cross-sectional (n=99) and a prospective study (n=221) of trauma survivors. RESULTS: Participants with acute stress disorder (ASD) or PTSD, but not trauma survivors without these disorders, identified trauma-related pictures, but not general threat pictures, better than neutral pictures. There were no group differences in the rate of trauma-related answers to other picture categories. The relative processing advantage for trauma-related pictures correlated with re-experiencing and dissociation, and predicted PTSD at follow-up. CONCLUSIONS: A perceptual processing bias for trauma-related stimuli may contribute to the involuntary triggering of intrusive trauma memories in PTSD.

[Reimbursement of new medical therapy]. / Erstattungsfähigkeit neuartiger Arzneimitteltherapien.

Medical progress poses a new financial challenge for the German statutory health insurance. In order to assure the stability of the German statutory health insurance all services have to be economical, but on the other hand the health care system allows access to new therapy in the ambulant and in-patient sector. This article describes in detail how new therapies are reimbursed.

Outreach and screening following the 2005 London bombings: usage and outcomes.

BACKGROUND: Little is known about how to remedy the unmet mental health needs associated with major terrorist attacks, or what outcomes are achievable with evidence-based treatment. This article reports the usage, diagnoses and outcomes associated with the 2-year Trauma Response Programme (TRP) for those affected by the 2005 London bombings.MethodFollowing a systematic and coordinated programme of outreach, the contact details of 910 people were obtained by the TRP. Of these, 596 completed a screening instrument that included the Trauma Screening Questionnaire (TSQ) and items assessing other negative responses. Those scoring ≥6 on the TSQ, or endorsing other negative responses, received a detailed clinical assessment. Individuals judged to need treatment (n=217) received trauma-focused cognitive-behaviour therapy (TF-CBT) or eye movement desensitization and reprocessing (EMDR). Symptom levels were assessed pre- and post-treatment with validated self-report measures of post-traumatic stress disorder (PTSD) and depression, and 66 were followed up at 1 year. RESULTS: Case finding relied primarily on outreach rather than standard referral pathways such as primary care. The effect sizes achieved for treatment of DSM-IV PTSD exceeded those usually found in randomized controlled trials (RCTs) and gains were well maintained an average of 1 year later. CONCLUSIONS: Outreach with screening, linked to the provision of evidence-based treatment, seems to be a viable method of identifying and meeting mental health needs following a terrorist attack. Given the failure of normal care pathways, it is a potentially important approach that merits further evaluation.

Mind the gap: Improving the dissemination of CBT.

Empirically supported psychological treatments have been developed for a range of psychiatric disorders but there is evidence that patients are not receiving them in routine clinical care. Furthermore, even when patients do receive these treatments there is evidence that they are often not well delivered. The aim of this paper is to identify the barriers to the dissemination of evidence-based psychological treatments and then propose ways of overcoming them, hence potentially bridging the gap between research findings and clinical practice.

Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.

A unique feature of the tumor cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA methylation, are involved in this silencing of many B-cell-associated genes. Here, we show that DNA demethylation alone or in conjunction with histone acetylation is not able to reconstitute the B-cell-gene expression program in cultured HRS cells. Instead, combined DNA demethylation and histone acetylation of B-cell lines induce an almost complete extinction of their B-cell-expression program and a tremendous upregulation of numerous Hodgkin-characteristic genes, including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the upregulation of Hodgkin-characteristic genes and the extinction of the B-cell-expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic upregulation of Hodgkin-characteristic genes thus plays--in addition to promoter DNA hypermethylation of B-cell-associated genes--a pivotal role for the reprogramming of HRS cells and explains why DNA demethylation alone is unable to reconstitute the B-cell-expression program in HRS cells.