Barriers and facilitators to social prescribing in child and youth mental health: perspectives from the frontline.

There is growing interest in the role of Social Prescribing (SP) to help promote mental well-being and support individuals with mental health difficulties. Yet, implementation of SP to children and young people (CYP) has proved slow and underdeveloped compared with adult populations. Understanding the barriers and facilitators will help key stakeholders to better embed SP for CYP into practice. Using the Theoretical Domains Framework (TDF), a comprehensive, theoretical-led framework, underpinned by 33 behaviour change theories and 128 constructs, perceived barriers and facilitators to SP were investigated. The sample comprised of 11 Link Workers and 9 individuals involved in facilitating SP with CYP, who took part in semi-structured interviews. Transcripts were analysed using a deductive thematic analysis, and themes were coded under each theoretical domain. Overall, 33 barriers and facilitators for SP were identified across 12 domains of the TDF. Under capability, barriers and facilitators were found for knowledge, skills, memory/attention/decision making processes, and behavioural regulation. For opportunity, barriers and facilitators were found for social/professional influences, as well as environmental context and resources. Finally, for motivation, domains covered included: beliefs about consequences, beliefs about capabilities, optimism, motivations/goals, reinforcement, and emotions. Findings suggest that a wide range of barriers and facilitators affect the implementation of CYP SP to improve mental health and well-being. Interventions which target different domains related to capability, opportunity and motivation should be developed to better facilitate CYP SP.

The TOR concept (training, operation, and rehabilitation) applied to a cohort of postpartum women with training-resistant symptomatic rectus diastasis: evaluation 1 year after surgery.

BACKGROUND: Rectus diastasis is a common sequela of pregnancy and is associated with functional disabilities such as back pain, abdominal core instability, abdominal muscle weakness, urinary incontinence, and psychological issues such as a negative body image. The aim of this study was to evaluate the effect of the TOR concept (training, operation, and rehabilitation), a novel concept for treating abdominal wall insufficiency combined with rectus diastasis, after pregnancy. TOR consists of preoperative evaluation of symptoms and custom-designed abdominal core training, tailored rectus diastasis repair, and individual progressive postoperative rehabilitation. METHODS: A consecutive series of women diagnosed with rectus diastasis and core dysfunction resistant to training, underwent plication of the linea alba between 2018 and 2020. After surgery, all patients participated in an individually designed rehabilitation programme over a 4-month interval. Physical function was recorded before surgery and 1 year after surgery using the disability rating index questionnaire. Symptoms associated with core instability were recorded before and 1 year after surgery. Quality of life was assessed using the SF-36. The abdominal wall anatomy was assessed with ultrasound before and 1 year after surgery. RESULTS: Seventy-one women were included and all attended 1-year follow-up. Response rate was 81.7 per cent (58) for the disability rating index, and 59.2 per cent (42) for SF-36. Self-reported physical function (disability rating index) improved in 54 of 58 patients (93.1 per cent), with a median score reduction of 91.3 per cent. Core instability symptoms decreased significantly. All SF-36 subscales improved significantly compared with preoperative scores, reaching levels similar to or higher than the normative Swedish female population. No recurrence of rectus diastasis was seen at the 1-year follow-up. CONCLUSIONS: Surgical reconstruction within the TOR concept resulted in significant improvements in physical function and quality of life as well as a significant decrease in symptoms of core instability.

Do postoperative complications correlate to chronic pain following inguinal hernia repair? A prospective cohort study from the Swedish Hernia Register.

PURPOSE: To analyse if postoperative complications constitute a predictor for the risk of developing long-term groin pain. METHODS: Population-based prospective cohort study of 30,659 patients operated for inguinal hernia 2015-2017 included in the Swedish Hernia Register. Registered post-operative complications were categorised into hematomas, surgical site infections, seromas, urinary tract complications, and acute post-operative pain. A questionnaire enquiring about groin pain was distributed to all patients 1 year after surgery. Multivariable logistic regression analysis was used to find any association between postoperative complications and reported level of pain 1 year after surgery. RESULTS: The response rate was 64.5%. In total 19,773 eligible participants responded to the questionnaire, whereof 73.4% had undergone open anterior mesh repair and 26.6% had undergone endo-laparoscopic mesh repair. Registered postoperative complications were: 750 hematomas (2.3%), 516 surgical site infections (1.6%), 395 seromas (1.2%), 1216 urinary tract complications (3.7%), and 520 hernia repairs with acute post-operative pain (1.6%). Among patients who had undergone open anterior mesh repair, an association between persistent pain and hematomas (OR 2.03, CI 1.30-3.18), surgical site infections (OR 2.18, CI 1.27-3.73) and acute post-operative pain (OR 7.46, CI 4.02-13.87) was seen. Analysis of patients with endo-laparoscopic repair showed an association between persistent pain and acute post-operative pain (OR 9.35, CI 3.18-27.48). CONCLUSION: Acute postoperative pain was a strong predictor for persistent pain following both open anterior and endo-laparoscopic hernia repair. Surgical site infection and hematoma were predictors for persistent pain following open anterior hernia repair, although the rate of reported postoperative complications was low.

Reference Data on the Normal Abdominal Wall Anatomy and Baseline Characteristics in Seventy-One Nulliparous Women.

Aims: The aim of this study was to describe the prepartum anatomy of the abdominal wall in a cohort of nulliparous women, for use as a reference for management of patients with postpartum abdominal wall insufficiency with or without rectus diastasis. Materials and Methods: Seventy-one women were examined with ultrasonography of the abdominal wall. The inter-recti distance (IRD), anatomical variations of the linea semilunaris, and the oblique muscles were assessed. The waistline was measured during activation and relaxation of the abdominal core. Participant characteristics were registered. Questionnaires regarding habitual physical activity (Baecke), low back pain (Oswestry), physical functioning (DRI), urinary incontinence (UDI-6 and IIQ-7), and quality-of-life (SF-36) were answered. Results: Mean age was 30.5 years (range 19-50 years) and mean BMI 23.5 kg/m2 (range 18-37). Ultrasonography showed a mean IRD of 10 mm (range 3-24) at the superior border of the umbilicus, 9 mm (4-20) 3 cm above the umbilicus, and 2 mm (-5-10) 2 cm below the umbilicus. The mean thickness of the linea alba was 3 mm (1.5-5) and mean distances between the lateral edge of the rectus muscle and the external, internal, and transverse oblique muscles were 12 mm (-10-28), 1 mm (-14-13) and 15 mm (-14-32) at umbilicus level. Responses to the DRI, UDI-6, IIQ-7 and Oswestry questionnaires showed generally lower scores than the normal population whereas Baecke and SF-36 scores were similar. Conclusion: This study provides baseline data on normal abdominal wall anatomy in a healthy nulliparous female cohort, as well as levels of activity, physical function, disability, and quality-of-life.

COVID-19 conspiracy ideation is associated with the delusion proneness trait and resistance to update of beliefs.

The rapid spread of conspiracy ideas associated with the recent COVID-19 pandemic represents a major threat to the ongoing and coming vaccination programs. Yet, the cognitive factors underlying the pandemic-related conspiracy beliefs are not well described. We hypothesized that such cognitive style is driven by delusion proneness, a trait phenotype associated with formation of delusion-like beliefs that exists on a continuum in the normal population. To probe this hypothesis, we developed a COVID-19 conspiracy questionnaire (CCQ) and assessed 577 subjects online. Their responses clustered into three factors that included Conspiracy, Distrust and Fear/Action as identified using principal component analysis. We then showed that CCQ (in particular the Conspiracy and Distrust factors) related both to general delusion proneness assessed with Peter's Delusion Inventory (PDI) as well as resistance to belief update using a Bias Against Disconfirmatory Evidence (BADE) task. Further, linear regression and pathway analyses suggested a specific contribution of BADE to CCQ not directly explained by PDI. Importantly, the main results remained significant when using a truncated version of the PDI where questions on paranoia were removed (in order to avoid circular evidence), and when adjusting for ADHD- and autistic traits (that are known to be substantially related to delusion proneness). Altogether, our results strongly suggest that pandemic-related conspiracy ideation is associated with delusion proneness trait phenotype.

Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress.

Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.

Association Between Inter-Recti Distance and Impaired Abdominal Core Function in Post-Partum Women With Diastasis Recti Abdominis.

Background and Aim: The definition and management of Diastasis Recti Abdominis (DRA) is under debate. This study aimed to understand the correlation between the post-partum inter-recti distance (IRD) and functional impairments associated with core instability, with the hypothesis that IRD could serve as a proxy for core instability symptoms and constitute a tool in decision-making for DRA treatment. Material and Methods: A cohort of post-partum women with abdominal core instability symptoms combined with DRA were studied. The size of IRD was measured with ultrasonography and cross-sectionally analysed against functional impairments registered with the self-report Disability Rating Index (DRI), which grades the ability to perform 12 different daily activities. Results: A total of 224 women were included in the study. In univariable analysis, IRD was associated with impairment of the activities running (p = 0.007), heavy work (p = 0.036) and exercise/sports (p = 0.047), but not with dressing, walking, sitting for long periods, standing bent over a sink, carrying a suitcase, making a bed, light manual labour or heavy lifting. No significant correlations were seen in the multivariable analysis when adjustments were made for BMI and parity. Conclusion: IRD and post-partum functional impairments had no significant correlation in multivariable analysis. The post-partum core instability condition is complex and probably associated with more factors than solely the IRD. The IRD alone does not seem to be a sufficient proxy for decision-making regarding optimal treatment. A more complete instrument to assess the post-partum abdominal core is warranted.

The association of selected multiple sclerosis symptoms with disability and quality of life: a large Danish self-report survey.

BACKGROUND: People with multiple sclerosis (MS) experience a wide range of unpredictable and variable symptoms. The symptomatology of MS has previously been reported in large sample registry studies; however, some symptoms may be underreported in registries based on clinician-reported outcomes and how the symptoms are associated with quality of life (QoL) are often not addressed. The aim of this study was to comprehensively evaluate the frequency of selected MS related symptoms and their associations with disability and QoL in a large self-report study. METHODS: We conducted a cross-sectional questionnaire survey among all patients at the Danish Multiple Sclerosis Center, Copenhagen University Hospital, Denmark. The questionnaire included information on clinical and sociodemographic characteristics, descriptors of QoL and disability, as well as prevalence and severity of the following MS symptoms: impaired ambulation, spasticity, chronic pain, fatigue, bowel and bladder dysfunction, and sleep disturbances. RESULTS: Questionnaires were returned by 2244/3606 (62%). Participants without MS diagnosis or incomplete questionnaires were excluded, n = 235. A total of 2009 questionnaires were included for analysis (mean age 49.4 years; mean disease duration 11.7 years; and 69% were women). The most frequently reported symptoms were bowel and bladder dysfunction (74%), fatigue (66%), sleep disturbances (59%), spasticity (51%) and impaired ambulation (38%). With exception of fatigue and sleep disturbances, all other symptoms increased in severity with higher disability level. Invisible symptoms (also referred to as hidden symptoms) such as fatigue, pain and sleep disturbances had the strongest associations with the overall QoL. CONCLUSION: We found invisible symptoms highly prevalent, even at mild disability levels. Fatigue, pain and sleep disturbances had the strongest associations with the overall QoL and were more frequently reported in our study compared with previous registry-based studies. These symptoms may be underreported in registries based on clinician reported outcomes, which emphasizes the importance of including standardized patient reported outcomes in nationwide registries to better understand the impact of the symptom burden in MS.

Circulating levels of tight junction proteins in multiple sclerosis: Association with inflammation and disease activity before and after disease modifying therapy.

BACKGROUND: Tight junction proteins contribute to maintenance of epithelial and endothelial barriers such as the intestinal barrier and the blood brain barrier (BBB). Increased permeability of these barriers has been linked to disease activity in MS and there is currently a lack of easily accessible biomarkers predicting disease activity in MS. AIM: To investigate whether levels of circulating tight junction proteins occludin and zonula occludens-1 (ZO-1) are associated with biomarkers of inflammation and disease activity; and to determine whether they could serve as clinical biomarkers. METHODS: We prospectively included 72 newly diagnosed patients with relapsing remitting MS or clinically isolated syndrome with no prior disease modifying therapy (DMT) use and 50 healthy controls (HCs). Patients were followed with blood samples, 3 tesla MRI, and clinical evaluation for 12 months. Occludin, ZO-1, calprotectin and soluble urokinase-type plasminogen activator receptor (suPAR) were measured by ELISA; serum neurofilament light (NfL) and IL-6 by single-molecule array (SIMOA). The mRNA expression of IFNG, IL1R1, IL10, IL1B, ARG1 and TNF was measured by quantitative real time polymerase chain reaction (qPCR) in whole blood. RESULTS: Plasma occludin levels were higher in MS patients compared with HCs. After 12 months on DMT, occludin levels were reduced by approximately 25% irrespective of 1st or 2nd line DMT (p<0.001). Furthermore, NfL and calprotectin levels were significantly reduced by 31% and 29%, respectively. Occludin and ZO-1 did not correlate with biomarkers of inflammation and did not predict disease activity at baseline or after 12 months. CONCLUSIONS: Higher levels of occludin suggest an increased permeability of the BBB and/or the intestinal barrier in MS patients. The reduction of occludin after 12 months on DMTs might reflect repair of these barriers upon treatment. However, plasma levels of ZO-1 and occludin could not predict clinical or MRI disease activity as determined by regression and ROC-curve analysis. Our results do not indicate a clear clinically relevant role for circulating tight junction proteins as biomarkers of disease activity in MS and further investigations in larger cohorts are needed to clarify this issue.

Psychedelic drug use and schizotypy in young adults.

Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18-35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen's d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen's d = 0.13) and a higher sensitivity of fear responses (Cohen's d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.

Evaluation of functional outcomes following rectus diastasis repair-an up-to-date literature review.

INTRODUCTION: Over the last decade rectus diastasis has gained attention as a condition that may benefit from surgery. Numerous surgical techniques have been presented but scientifically proper studies reporting functional outcome are few and evidence is incomplete. The aim of this up-to-date review is to analyse the outcomes of rectus diastasis repair in recently published papers, focusing on functional changes following surgery. METHOD: A comprehensive search in PubMed and Web of Science was performed. Suitable papers were selected using titles and abstracts with terms suggesting surgical treatment of rectus diastasis. All abstracts were scrutinised, and irrelevant studies excluded in four stages. Reports providing original data, including outcome assessment following surgery, were included. RESULT: Ten papers with a total of 780 patients were found to fulfil the search criteria. Study design, surgical procedure, follow-up time, functional outcome and assessment instruments were compiled. All included studies reported improvements in a variety of functional aspects regardless of surgical method. The outcomes assessed include core stability, back pain, abdominal pain, posture, urinary incontinence, abdominal muscle strength and quality of life. CONCLUSION: The results of this review show that surgical repair of rectus diastasis is a safe and effective treatment that improves functional disability. However, the absence of standardized instruments for assessing outcome makes it impossible to compare studies. Since indications for surgery are relative and related to core function, valid instruments for assessing indication and outcome are needed to ensure benefit of the procedure.

Three-dimensional reconstruction of porous polymer films from FIB-SEM nanotomography data using random forests.

Combined focused ion beam and scanning electron microscope (FIB-SEM) tomography is a well-established technique for high resolution imaging and reconstruction of the microstructure of a wide range of materials. Segmentation of FIB-SEM data is complicated due to a number of factors; the most prominent is that for porous materials, the scanning electron microscope image slices contain information not only from the planar cross-section of the material but also from underlying, exposed subsurface pores. In this work, we develop a segmentation method for FIB-SEM data from ethyl cellulose porous films made from ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. These materials are used for coating pharmaceutical oral dosage forms (tablets or pellets) to control drug release. We study three samples of ethyl cellulose and hydroxypropyl cellulose with different volume fractions where the hydroxypropyl cellulose phase has been leached out, resulting in a porous material. The data are segmented using scale-space features and a random forest classifier. We demonstrate good agreement with manual segmentations. The method enables quantitative characterization and subsequent optimization of material structure for controlled release applications. Although the methodology is demonstrated on porous polymer films, it is applicable to other soft porous materials imaged by FIB-SEM. We make the data and software used publicly available to facilitate further development of FIB-SEM segmentation methods. LAY DESCRIPTION: For imaging of very fine structures in materials, the resolution limits of, e.g. X-ray computed tomography quickly become a bottleneck. Scanning electron microscopy (SEM) provides a way out, but it is essentially a two-dimensional imaging technique. One manner in which to extend it to three dimensions is to use a focused ion beam (FIB) combined with a scanning electron microscopy and acquire tomography data. In FIB-SEM tomography, ions are used to perform serial sectioning and the electron beam is used to image the cross section surface. This is a well-established method for a wide range of materials. However, image analysis of FIB-SEM data is complicated for a variety of reasons, in particular for porous media. In this work, we analyse FIB-SEM data from ethyl cellulose porous films made from ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. These films are used as coatings for controlled drug release. The aim is to perform image segmentation, i.e. to identify which parts of the image data constitute the pores and the solid, respectively. Manual segmentation, i.e. when a trained operator manually identifies areas constituting pores and solid, is too time-consuming to do in full for our very large data sets. However, by performing manual segmentation on a set of small, random regions of the data, we can train a machine learning algorithm to perform automatic segmentation on the entire data sets. The method yields good agreement with the manual segmentations and yields porosities of the entire data sets in very good agreement with expected values. The method facilitates understanding and quantitative characterization of the geometrical structure of the materials, and ultimately understanding of how to tailor the drug release.

Biomarkers of inflammation and epithelial barrier function in multiple sclerosis.

BACKGROUND: There is a lack of reliable biomarkers predicting disability and disease activity in multiple sclerosis (MS). Recent evidence suggests an involvement of intestinal and pulmonary epithelial barrier function related to immune activation and the pathophysiology of MS. Blood biomarkers of epithelial barrier function have, however, not been widely studied in MS. OBJECTIVE: To examine biomarkers of inflammation and epithelial barrier function in relapsing remitting MS (RRMS) patients compared with healthy controls (HCs), and to assess associations between biomarkers and disease activity. METHODS: A panel of 30 biomarkers were measured in serum or plasma from 49 newly diagnosed, untreated RRMS patients and 58 HCs with electrochemiluminescence or ELISA. Neurofilament light chain (NfL) was measured with single-molecule array. Validation was performed in a second independent cohort of 68 newly diagnosed, treatment naive RRMS patients and 50 HCs. Patients were divided into groups of active and inactive disease based on NfL levels and the presence of gadolinium enhancing magnetic resonance imaging lesions. RESULTS: Patients with active MS showed significantly higher serum levels of calprotectin and soluble urokinase plasminogen activator receptor compared with inactive MS in the exploratory cohort. Validation confirmed higher levels of calprotectin in active compared with inactive MS, and HCs. Biomarkers of intestinal and pulmonary epithelial barrier function did not differ significantly between groups. CONCLUSIONS: The measured biomarkers of epithelial barrier function do not seem to play a major role in the pathophysiology of MS, but serum calprotectin could represent a clinically useful biomarker of innate immune activation and disease activity.

3D high spatial resolution visualisation and quantification of interconnectivity in polymer films.

A porous network acts as transport paths for drugs through films for controlled drug release. The interconnectivity of the network strongly influences the transport properties. It is therefore important to quantify the interconnectivity and correlate it to transport properties for control and design of new films. This work presents a novel method for 3D visualisation and analysis of interconnectivity. High spatial resolution 3D data on porous polymer films for controlled drug release has been acquired using a focused ion beam (FIB) combined with a scanning electron microscope (SEM). The data analysis method enables visualisation of pore paths starting at a chosen inlet pore, dividing them into groups by length, enabling a more detailed quantification and visualisation. The method also enables identification of central features of the porous network by quantification of channels where pore paths coincide. The method was applied to FIB-SEM data of three leached ethyl cellulose (EC)/hydroxypropyl cellulose (HPC) films with different weight percentages. The results from the analysis were consistent with the experimentally measured release properties of the films. The interconnectivity and porosity increase with increasing amount of HPC. The bottleneck effect was strong in the leached film with lowest porosity.

Comparison of Two Information Sources for Cause-of-Death Follow-up in the Russian Federation: The Asbest Chrysotile Cohort Study.

BACKGROUND: The Asbest chrysotile cohort was set up in Asbest town, Sverdlovsk oblast, Russian Federation, among the current and former workforce of the world's largest operating chrysotile mine and its processing mills, to investigate cancer risk in relation to occupational exposure to chrysotile. OBJECTIVES: The cohort of 35,837 people was followed-up for mortality using cause-of-death information from official death certificates issued by the Civil Act Registration Office (ZAGS) of Sverdlovsk oblast from 1976 to 2015. Data were also retrieved from the electronic cause-of-death registry of the Medical Information Analytical Centre (MIAC) of Sverdlovsk oblast, which was launched in 1990 and operates independently of ZAGS. The objectives were to compare the completeness of record linkage (RL) with ZAGS and with MIAC, and to compare the agreement of cause-of-death information obtained from ZAGS and from MIAC, with a focus on malignant neoplasms. METHODS: RL completeness of identifying cohort members in ZAGS and in MIAC was compared for the period 1990 to 2015. In the next step, for the comparison of the retrieved cause-of-death information, 5,463 deaths (1,009 from cancer) were used that were registered in 2002 to 2015, when causes of death were coded using International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) nomenclature by MIAC. For ZAGS, original cause-of-death text from the death certificates was obtained and then coded according to ICD-10 by the International Agency for Research on Cancer/World Health Organization (IARC/WHO). Agreement was evaluated at various levels of detail, and reasons for any disagreements between the MIAC and the IARC/WHO ICD-10-coded cancer diagnosis were systematically explored. RESULTS: A total of 10,886 deaths were obtained from all avenues of follow-up for the period 1990 to 2015 in the cohort; 10,816 (99.4%) of these were found in ZAGS. This percentage was 88.3% if only automated deterministic RL was used and 99.4% when deterministic RL was complemented with manual searches of cohort members. Comparison of the cause-of-death information showed agreement of 97.9% at the ICD-10 main group level between ZAGS (coded by IARC/WHO) and MIAC. Of 1,009 cancer deaths, 679 (67.3%) cases had identical coding, 258 (25.6%) cases corresponded at the three-character ICD-10 level, 36 (3.6%) had codes that were within the same anatomical or morphological cluster, and for only 36 (3.6%) cases were major discrepancies identified. Altogether, the agreement between IARC/WHO coding of cause-of-death information from ZAGS and MIAC coding of malignant neoplasms was therefore 96.4%. CONCLUSIONS: RL completeness and agreement of cause-of-death information obtained from ZAGS and from MIAC were both very high. This is reassuring for the quality of cancer mortality follow-up of the Asbest chrysotile cohort. For future epidemiological studies in the Russian Federation, ZAGS appears to be a reliable information source for mortality follow-up, if the automated RL is complemented with manual searches of cohort members. MIAC is a good resource for prospective studies.

Evaluation of polymyxin B in combination with 13 other antibiotics against carbapenemase-producing Klebsiella pneumoniae in time-lapse microscopy and time-kill experiments.

OBJECTIVES: This study aimed to explore the interactions of polymyxin B in combination with 13 other antibiotics against carbapenemase-producing Klebsiella pneumoniae. METHODS: Five clinical isolates of multidrug-resistant K. pneumoniae producing KPC-2, KPC-3, NDM-1, OXA-48 and VIM-1 carbapenemases were used. Polymyxin B was tested alone and in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, linezolid, meropenem, minocycline, rifampicin, temocillin, thiamphenicol and trimethoprim. Inhibition of growth during antibiotic exposure was evaluated in 24-hr automated time-lapse microscopy experiments. Combinations that showed positive interactions were subsequently evaluated in static time-kill experiments. RESULTS: All strains carried multiple (≥9) resistance genes as determined by whole-genome sequencing. In the initial screening the combination of polymyxin B and minocycline was most active with enhanced activity compared with the single antibiotics detected against all strains. Positive interactions were also observed with polymyxin B in combination with rifampicin and fosfomycin against four of five strains and less frequently with other antibiotics. Time-kill experiments demonstrated an additive or synergistic activity (1-2 log10 or ≥2 log10 CFU/mL reduction, respectively, compared with the most potent single antibiotic) with 21 of 23 tested combinations. However, because of regrowth, only 13 combinations were synergistic at 24 hr. Combinations with minocycline or rifampicin were most active, each showing synergy and bacteriostatic or bactericidal effects resulting in 1.93-3.97 and 2.55-5.91 log10 CFU/mL reductions, respectively, after 24 hr against four strains. DISCUSSION: Polymyxin B in combination with minocycline, rifampicin or fosfomycin could be of potential clinical interest. Time-lapse microscopy showed some discrepancy in results compared with the time-kill data but was useful for screening purposes.

Cohort study of the effect of surgical repair of symptomatic diastasis recti abdominis on abdominal trunk function and quality of life.

Background: During pregnancy, women are at risk of developing persistent symptomatic diastasis recti abdominis (DRA), which may have a detrimental effect on their physical function and quality of life (QoL). The aim of this prospective cohort study was to determine the effect of surgical repair of DRA on abdominal trunk function, urinary incontinence and QoL in postpartum women with trunk instability symptoms resistant to training. Methods: Postpartum women with diagnosed DRA and training-resistant symptoms underwent double-row plication of the linea alba. Abdominal trunk function was evaluated as the primary endpoint using a multimodal examination tool, the Abdominal Trunk Function Protocol. Recurrence was assessed by CT, urinary incontinence was evaluated using the Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7), and QoL was assessed with the Short Form 36 (SF-36®) questionnaire. All subjects were examined before and 1 year after surgery. Results: Sixty women were recruited. There was no DRA recurrence at the 1-year follow-up. Self-reported abdominal trunk function had improved in 98 per cent of patients, with a mean score improvement of 79·1 per cent. In the physiological tests monitored by a physiotherapist, 76 per cent performed better and endured exercise tests longer than before surgery. All SF-36® subscales improved significantly compared with preoperative scores and reached levels similar to, or higher than, the normative Swedish female population. For the UDI-6 and IIQ-7, 47 and 37 per cent respectively reported fewer symptoms at follow-up than before surgery, and 13 and 8 per cent respectively reported more symptoms. Conclusion: In this series of postpartum women presenting with DRA and symptoms of trunk instability resistant to training, surgical reconstruction resulted in a significant improvement in abdominal trunk function, urinary incontinence and QoL.

Antecedentes: Durante el embarazo, las mujeres tienen el riesgo de desarrollar una diástasis rectoabdominal persistente y sintomática (diastasis rectoabdominis, DRA) que puede tener un efecto perjudicial en su función física y en la calidad de vida (quality of life, QoL). El objetivo de este estudio de cohortes prospectivo fue determinar el efecto de reparación quirúrgica de la DRA en la función de la musculatura de la pared abdominal, la incontinencia urinaria y la QoL en mujeres con síntomas postparto de inestabilidad de la musculatura abdominal resistentes al entrenamiento. Métodos: Sesenta mujeres diagnosticadas en el postparto de DRA y con síntomas resistentes al entrenamiento se sometieron a una plicatura de doble capa de la línea alba. El objetivo primario fue evaluar la función de la musculatura de la pared abdominal mediante una herramienta de examen multimodal, el protocolo de la función de la pared abdominal (abdominal trunk function protocol, ATFP). La recidiva se evaluó mediante tomografía computarizada, la incontinencia urinaria utilizando los cuestionarios UDI­6 y IIQ­7 y la calidad de vida con el cuestionario SF­36. Todas las participantes fueron examinadas antes de la cirugía y un año después de la misma. Resultados: Tras un año de seguimiento, no hubo recidiva de la DRA. Según informaron las pacientes, la función de la musculatura abdominal había mejorado en el 98,2% de los casos, con una mejoría en la puntuación media del 79,1%. En las pruebas fisiológicas controladas por un fisioterapeuta, el 76,0% presentó mejoría y aumentó la duración en las pruebas de resistencia en comparación con antes de la cirugía. Todas las subescalas del SF­36 mejoraron significativamente en comparación con las puntuaciones preoperatorias y alcanzaron niveles similares o superiores a los de la población femenina sueca normal. Para el UDI­6 y el IIQ­7, el 46,7% y el 36,7% respectivamente, manifestaron menos síntomas en el seguimiento que antes de la cirugía, mientras que el 13,3% y el 8,3% respectivamente, reportaron más síntomas. Conclusión: En esta serie de mujeres que presentan DRA en el posparto y síntomas de inestabilidad de la musculatura abdominal resistente al entrenamiento, la reconstrucción quirúrgica produjo una mejora significativa en la función de la musculatura abdominal, la incontinencia urinaria y la calidad de vida.

Activated platelet aggregation is transiently impaired also by a reduced dose of protamine.

Objectives: Protamine reduces platelet aggregation after cardiopulmonary bypass (CPB). We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and the possible correlation to postoperative bleeding. Design: Platelet function was assessed by impedance aggregometry in 30 patients undergoing cardiac surgery with CPB at baseline, before protamine administration, after 70% and 100% of the calculated protamine dose, after 20 minutes and at arrival to the intensive care unit. Adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used as activators. Blood loss was measured during operation and three hours after surgery. Results are presented as median (25th-75th percentile). Results: Platelet aggregation decreased markedly after the initial dose of protamine (70%) with all activators; ADP 89 (71-110) to 54 (35-78), TRAP 143 (116-167) to 109 (77-136), both p < .01; AA 25 (16-49) to 17 (12-24) and COL 92 (47-103) to 60 (38-81) U, both p < .05. No further decrease was seen after 100% protamine. The effect was transient and after twenty minutes platelet aggregation had started to recover; ADP 76 (54-106), TRAP 138 (95-158), AA 20 (10-35), COL 70 (51-93) U. Blood loss during operation correlated to aggregometry measured at baseline and after protaminization. Conclusions: Protamine after CPB induces a marked decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1. The impairment seems to be transient and recovery had started after 20 minutes.

The neutrophil-to-lymphocyte ratio is associated with multiple sclerosis.

BACKGROUND: Subtypes of white blood cell counts are known biomarkers of systemic inflammation and a high neutrophil-to-lymphocyte ratio (NLR) has been associated with several autoimmune diseases. Few studies have investigated the NLR in multiple sclerosis (MS). OBJECTIVE: To examine the association between NLR, MS and disability measured by the MS severity score (MSSS). METHODS: Patients were included from the Danish Multiple Sclerosis Biobank. Information on patient NLR was obtained just before their first treatment and clinical information was provided by the Danish Multiple Sclerosis Treatment Register. Information on NLR from controls was collected from the Danish Blood Donor Study. Patients and controls were 1:2 propensity score matched by baseline confounders. RESULTS: Propensity score matching left 740 of 743 MS patients and 1420 of 4691 controls for further analyses. Odds-ratio (OR) was 3.64 (95% confidence interval 2.87-4.60, p < 0.001) for MS disease per unit increase of logarithmically transformed NLR (ln-NLR), corresponding to an OR of 2.68 for each doubling of NLR. Mean NLR was 2.12 for patients and 1.72 for controls (p < 0.001). Ln-NLR correlated weakly with patient MSSS (R 2 = 0.019, p = 0.008). CONCLUSION: Patients with early MS had increased levels of NLR compared to healthy controls and NLR was weakly correlated with MSSS.