A comparison of the breast milk microbiota from women diagnosed with gestational diabetes mellitus and women without gestational diabetes mellitus.

BACKGROUND: Human breast milk (HBM) is a contributing factor in modulating the infant's gut microbiota, as it contains bacteria that are directly transferred to the infant during breastfeeding. It has been shown that children of women diagnosed with gestational diabetes mellitus (GDM) have a different gut microbiota compared to children of women without GDM. Our hypothesis is therefore that women with GDM have a different HBM microbiota, which may influence the metabolic function and capacity of the child later in life. The aim of this study was to investigate whether women with GDM have a different breast milk microbiota 1-3 weeks postpartum compared to women without GDM. METHODS: In this case-control study, a total of 45 women were included: 18 women with GDM and 27 women without GDM. A milk sample was collected from each participant 1 to 3 weeks postpartum and the bacterial composition was examined by 16 S rRNA gene sequencing targeting the V4 region. RESULTS: High relative abundances of Streptococcus and Staphylococcus were present in samples from both women with and without GDM. No difference could be seen in either alpha diversity, beta diversity, or specific taxa between groups. CONCLUSION: Our results did not support the existence of a GDM-associated breast milk microbiota at 1-3 weeks postpartum. Further research is needed to fully understand the development of the gut microbiota of infants born to mothers with GDM.

Health literacy and cognitive function in people with diabetic foot ulcer with focus on knowledge, attitude, and practice in relation to foot self-care.

Introduction: Preventative foot self-care is vital for avoiding diabetic foot ulcer episodes and lowering the risk of amputations. Yet, it demands high levels of health literacy and cognitive function. Objective: To investigate health literacy and cognitive function in persons presenting with a diabetic foot ulcer. Methods: Participants with type 2 diabetes were recruited from the tertiary foot clinic at Steno Diabetes Center North Denmark. The European Health Literacy Survey Questionnaire and Addenbrooke's Cognitive Examination were applied. A semi-structured interview guide was developed to evaluate foot self-care knowledge, attitude, and practice. The qualitative data were analyzed with a deductive approach based on a qualitative thematic analysis model. Subsequently, an integrated analysis of the quantitative and qualitative results was conducted. Results: The participants (n = 12) had a mean age of 62.6 ± 8.4 years, and 11 were males. The mean diabetes duration was 15.9 ± 8.9 years. Eight participants had a recurrent diabetic foot ulcer. The health literacy level was sufficient in nine participants, and cognitive function was normal in five participants. Three different profiles related to foot self-care (proactive, active, or passive, respectively) were constructed by the final integrated analysis: a proactive profile refers to taking preventative action in concordance with knowledge and attitude, an active profile to taking action in response to a situation, but challenged by conflicting levels of knowledge and attitude, and a passive profile to not taking action. Conclusion: The study suggests that people presenting with a diabetic foot ulcer have different foot self-care profiles based on person-specific health literacy, cognitive function, and knowledge, attitude, and practice element characteristics, highlighting the need for individualized education and intervention strategy instead of a one-size-fits-all approach.

Cannabis medicine for chronic pain.

In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.

Naïve Inflammatory Proteome Profiles of Glucocorticoid Responsive Polymyalgia Rheumatica and Rheumatic Arthritis Patients-Links to Triggers and Proteomic Manifestations.

Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation.

Assessment of Human Fetuses Undergoing Acute Pain: Validation of the Fetal-7 Scale.

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often through surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved 2 steps: 1) 4 fetuses with the indication of surgery were evaluated in 3 conditions perioperatively: acute pain, rest, and under loud sound stimulation. Facial expressions were assessed by 30 raters using screenshots from 4D high-definition ultrasound films; 2) assessment of sensitivity and specificity of the Fetal-7 scale in 54 healthy fetuses and 2 fetuses undergoing acute pain after preoperative anesthetic intramuscular injection. There was high internal consistency with Cronbach's alpha (α) of .99. Intrarater reliability of the Fetal-7 scale (test-retest) calculated by intraclass correlation coefficient was .95, and inter-rater reliability was .99. The scale accurately differentiated between healthy fetuses at rest and those experiencing acute pain (sensitivity of 100% and specificity of 94.4%). The Fetal-7 scale is a valid tool for assessing acute pain-related behavior in third-trimester fetuses and may be of value in guiding analgesic procedures efficacy in these patients. Further research is warranted to explore the presence of postoperative pain in fetuses and its effects after birth. PERSPECTIVE: Recordings with 3-dimensional ultrasound of human fetuses undergoing preoperative anesthetic injections revealed complex facial expressions during acute pain, similar to those collected in newborns. This study presented the validation process and cut-off value of the Fetal-7 scale, paving the way for the study of pain before birth in humans.

A study on the risk stratification for patients within 24 hours of admission for risk of hospital-acquired urinary tract infection using Bayesian network models.

Early identification of patients at risk of hospital-acquired urinary tract infections (HA-UTI) enables the initiation of timely targeted preventive and therapeutic strategies. Machine learning (ML) models have shown great potential for this purpose. However, existing ML models in infection control have demonstrated poor ability to support explainability, which challenges the interpretation of the result in clinical practice, limiting the adaption of the ML models into a daily clinical routine. In this study, we developed Bayesian Network (BN) models to enable explainable assessment within 24 h of admission for risk of HA-UTI. Our dataset contained 138,250 unique hospital admissions. We included data on admission details, demographics, lifestyle factors, comorbidities, vital parameters, laboratory results, and urinary catheter. Models developed from a reduced set of five features were characterized by transparency compared to models developed from a full set of 50 features. The expert-based clinical BN model over the reduced feature space showed the highest performance (area under the curve = 0.746) compared to the naïve- and tree-augmented-naïve BN models. Moreover, models developed from expert-based knowledge were characterized by enhanced explainability.

Differences in bacterial taxa between treatment-naive patients with major depressive disorder and non-affected controls may be related to a proinflammatory profile.

BACKGROUND: Major depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been hypothesized to be involved in MDD through gut-brain axis signaling. Moreover, antidepressants display antibacterial properties in the gastrointestinal tract. The aim of this study was to compare the gut microbiota and systemic inflammatory profile of young patients with MDD before and after initiation of antidepressant treatment and/or psychotherapy in comparison with a non-depressed control group (nonMDD). METHODS: Fecal and blood samples were collected at baseline and at follow-up after four and twelve weeks, respectively. Patients started treatment immediately after collection of the baseline samples. The gut microbiota was characterized by 16 S rRNA gene sequencing targeting the hypervariable V4 region. Plasma levels of 49 unique immune markers were assessed using Mesoscale. RESULTS: In total, 27 MDD patients and 32 nonMDD controls were included in the study. The gut microbiota in the baseline samples of MDD versus nonMDD participants did not differ regarding α- or ß-diversity. However, there was a higher relative abundance of the genera Ruminococcus gnavus group, and a lower relative abundance of the genera Desulfovibrio, Tyzzerella, Megamonas, Olsenella, Gordonibacter, Allisonella and Rothia in the MDD group compared to the nonMDD group. In the MDD group, there was an increase in the genera Rothia, Desulfovibrio, Gordinobacteer and Lactobacillus, while genera belonging to the Firmicutes phylum were found depleted at twelve weeks follow-up compared to baseline. In the MDD group, IL-7, IL-8 and IL-17b levels were elevated compared to the nonMDD group at baseline. Furthermore, MDI score in the MDD group was found to correlate with Bray-Curtis dissimilarity at baseline, and several inflammatory markers at both baseline and after initiation of antidepressant treatment. CONCLUSION: Several bacterial taxa differed between the MDD group and the nonMDD group at baseline and changed in relative abundance during antidepressant treatment and/or psychotherapy. The MDD group was furthermore found to have a pro-inflammatory profile compared to the nonMDD group at baseline. Further studies are required to investigate the gut microbiota and pro-inflammatory profile of patients with MDD.

Impact of Low-Dose Dronabinol Therapy on Cognitive Function in Cancer Patients Receiving Palliative Care: A Case-Series Intervention Study.

Background: Cannabis may offer therapeutic benefits to patients with advanced cancer not responding adequately to conventional palliative treatment. However, tolerability is a major concern. Cognitive function is a potential adverse reaction to tetrahydrocannabinol containing regimens. The aim of this study was to test cognitive function in patients being prescribed dronabinol as an adjuvant palliative therapy. Methods: Adult patients with advanced cancer and severe related pain refractory to conventional palliative treatment were included in this case-series study. Patients were examined at baseline in conjunction with initiation of dronabinol therapy and at a two-week follow-up using three selected Wechsler's adult intelligence scale III neurocognitive tests: Processing Speed Index (PSI), Perceptual Organization Index (POI), and Working Memory Index (WMI). Patients were also assessed using pain visual analog scale, Major Depression Inventory, and Brief Fatigue Inventory. Results: Eight patients consented to take part in the study. Two patients discontinued dronabinol therapy, one due to a complaint of dizziness and another critical progression of cancer disease, respectively. The remaining six patients were successfully treated with a daily dosage of 12.5 mg dronabinol (p = 0.039). PSI (p = 0.020), POI (p = 0.034.), and WMI (p = 0.039). Conclusions: Cognitive function improved in this group of patients with advanced cancer in conjunction with low-dose dronabinol therapy. The cause is likely multifactorial including reported relief of cancer-associated symptoms. Further clinical investigation is required.

Influenza Vaccine Type-Dependent Antibody Response in Patients with Autoimmune Inflammatory Rheumatic Diseases.

BACKGROUND: The study aimed to explore influenza antibody response in patients with autoimmune inflammatory rheumatoid diseases (AIIRDs) stratified by the different vaccine types applied in Denmark during the 2018-2019 influenza season. METHODS: Included patients were diagnosed with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis receiving biological disease-modifying antirheumatic drugs (bDMARDs) with or without conventional synthetic disease-modifying antirheumatic drugs. Influenza vaccination status in the 2018-2019 season and vaccine type received were reviewed in the Denmark. Blood samples were drawn ≥ 14 days post vaccination, and antibody titers were determined by the hemagglutinin inhibition (HAI) assay for the serotypes A/Michigan/H1N1, A/Singapore/H3N2, and B/Colorado included in the influenza vaccines in the 2018-2019 season. An overall serotype HAI geometric mean titer (GMT) was calculated from the 3 serotype-specific HAI titers. An overall serotype HAI GMT ≥ 40 was considered protective. RESULTS: Of the 205 included patients, 105 (51%) had received influenza vaccination. One-quarter of vaccinated patients achieved post-vaccination overall serotype HAI GMT ≥40. For patients vaccinated with Influvac, a significantly higher proportion had HAI titers ≥ 40 for 2 serotypes, namely, A/Michigan/H1N1 and A/Singapore/H3N2, than patients vaccinated with Vaxigrip or VaxigripTetra. The same applied to all serotypes HAI GMT, where significantly more patients who received Influvac achieved postvaccination HAI GMT≥40 versus patients who received Vaxigrip (p=0.02) or VaxigripTetra (p=0.002). The latter outcome was explored in a multivariable logistic regression analysis and remained significant when including the following variables: age, sex, treatment with methotrexate and/or prednisolone, type of influenza vaccine, time interval from vaccination to antibody measurement, and previous vaccination status. CONCLUSION: Influenza antibody levels following vaccination with Influvac in bDMARD-treated patients with AIIRDs were superior to Vaxigrip and VaxigripTetra. Treatment with methotrexate (MTX) did not reduce the antibody response.

Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This study investigates if fermented red clover isoflavones reduce OAB symptoms in postmenopausal women. In this randomized, double-blinded, placebo-controlled trial, women were administered red clover extract (RCE) or a placebo twice daily for three months. Women filled out the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and Urinary Incontinence Short Form (ICIQ-UI-SF), together with a fluid intake and voiding diary. A total of 33 women (16 in the RCE group and 17 in the placebo group) were included in the analysis. Baseline demographics and OAB characteristics were comparable across groups. Intake of RCE did not lead to significant relief in most urinary bladder symptom measures, although a significant reduction in the bother of urinary urgency (p = 0.033) and a tendency towards a decreased ICIQ-OAB score were observed (p = 0.056). In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes. We found that an intake of isoflavones did not relieve OAB symptoms in postmenopausal women.

Assessment of neuropsychiatric manifestations in a cohort of intensive care unit survivors: A proof of concept study.

The aim of this study was to assess the feasibility and outcome of a neuropsychiatric evaluation protocol intended for adult intensive care unit survivors in a Danish regional hospital, in which a follow-up consultation was conducted 2 months after hospital discharge. Twenty-three participants were able to finalize the neuropsychiatric evaluation, and 20 (87%) among those were detected with neuropsychiatric manifestations, including cognitive impairment (n = 17; 74%) and fatigue (n = 17, 74%). This study finds a high prevalence of neuropsychiatric manifestations and fatigue, and evaluates a follow-up protocol for the ICU patient population.

The urinary, vaginal and gut microbiota in women with genital lichen sclerosus - A case-control study.

BACKGROUND: Lichen sclerosus (LS) is a chronic, autoimmune skin disease predominantly located in the anogenital region in women. In recent years, the role of the human microbiota in the pathogenesis of autoimmune diseases, including LS, has received interest. OBJECTIVES: The study aimed to evaluate and compare the composition of the urinary, vaginal and gut microbiota in women with LS versus non-affected controls. STUDY DESIGN: Women diagnosed with LS (n = 16) and matched controls (n = 14) were enrolled in the study. From each participant, midstream urine, upper and lower vaginal swabs, as well as faecal samples, were collected. The microbiota composition was assessed using 16S ribosomal RNA (rRNA) gene sequencing of the V4 hypervariable region. RESULTS: We observed no LS-specific clustering in either of the four anatomic niches, using either hierarchical cluster analysis or weighted beta diversity metrics. However, for unweighted UniFrac, significant differences in the urinary and lower vaginal microbiota were observed when comparing women with LS to controls. These findings indicate that while the two groups have microbiota dominated by the same bacteria, variations do occur amongst less abundant bacteria. The LEfSe analysis revealed a higher relative abundance of the genus Streptococcus in the urinary and lower vaginal microbiota in women with LS compared to controls. Additionally, a higher relative abundance of phylum Euryarchaeota was observed in the gut microbiota in women with LS compared to controls. CONCLUSION: In this study, we demonstrated several differences amongst less abundant bacteria in the urinary, lower vaginal and faecal microbiota when comparing women with LS to controls. However, further research is required to assess whether these microbiota differences are causative or merely a result of the underlying LS disease.

Prospective pilot study on the relationship between seminal HIV-1 shedding and genital schistosomiasis in men receiving antiretroviral therapy along Lake Malawi.

Male genital schistosomiasis (MGS) is hypothesized to increase seminal shedding of HIV-1. This prospective pilot study assessed seminal HIV-1 RNA shedding in men on long-term ART with and without a diagnosis of MGS. Study visits occurred at 0, 1, 3, 6 and 12 months. MGS was diagnosed by egg positivity on semen microscopy or PCR of seminal sediment. After optimization of the HIV-RNA assay, we examined 72 paired plasma and semen samples collected from 31 men (15 with and 16 without MGS) over 12 months. HIV-1 RNA was detected in 7/72 (9.7%) seminal samples and 25/72 (34.7%) plasma samples. When comparing sample pairs, 5/72 (6.9%) showed HIV-1 RNA detection only in the seminal sample. Overall, 3/31 (9.7%) participants, all with MGS, had detectable HIV-1 RNA in semen while plasma HIV-1 RNA was undetectable (< 22 copies/mL), with seminal levels ranging up to 400 copies/mL. Two participants showing HIV-1 RNA in seminal fluid from the MGS-negative group also had concomitant HIV-1 RNA detection in plasma. The findings suggest that MGS can be associated with low-level HIV-1 RNA shedding despite virologically suppressive ART. Further studies are warranted to confirm these observations and assess its implications.

Short-term prognosis of changes in plasma potassium following an episode of hyperkalaemia in patients with chronic heart failure.

BACKGROUND/AIM: There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF. METHODS AND RESULTS: From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14-365 days from concomitant treatment were identified. To be included, a second measurement was required within 6-30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5-4.0 mmol/L (n = 709), 4.1-4.6 mmol/L (n = 1,204, reference), 4.7-5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49-3.70) and 3.5-4.0 mmol/L (HR: 1.81; 95% CI: 1.54-2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality. CONCLUSION: Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6-30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5-4.0 mmol/L).

Increasing use of computed tomography scans in the North Denmark Region raises patient safety concern.

PURPOSE: Use of computed tomography (CT) scans raises safety concern as lifetime cumulative ionising radiation exposure is associated with risk of developing malignancies. This study aimed to investigate use of abdominal CT scans in the Danish health care sector. METHODS: Data on abdominal CT scans performed annually in the North Denmark Region between 2005 and 2018 were extracted from the regional registry with emphasis on patients with a medical history of a repeated abdominal CT scan within 28 days. An audit of the medical files was subsequently conducted in 100 randomly selected patient cases to evaluate clinical information being provided, in addition to justification for a repeated abdominal CT scan, and finally if other radiology modalities could have been applied. RESULTS: Number of annually performed abdominal CT scans in this demographically stable regional population increased by a factor 4.3 from 15 in 2005 to 65 in 2018 per 1,000 inhabitants. The audit revealed that 31% of the secondabdominal CT scans within a 28 days period were categorized as either doubtful whether justified or not justified. Moreover, 20% of theCT scans were considered replaceable by ultrasonography. CONCLUSIONS: Annual performance of abdominal CT scans increased fourfold during the 14 years period. This tendency is probably attributable to changes in the Danish health care sector by which CT scan examination are used more frequently aiming at more accelerated patient investigation flow in conjunction with shorter length of hospitalization stay. Alertness is strongly warranted towards the associated risk of cancer due to life-time cumulative ionising radiation exposure by this strategy.

Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions.

An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.

Antibiotic Practice in Patients With Acute Abdomen Admitted to a Danish Regional Hospital: A Clinical Qualitative Assurance Study.

Background Acute abdomen is often complicated by intra-abdominal infection requiring antibiotic therapy. Danish regional antibiotic guidelines emphasize the restricted use of broad-spectrum antibiotics such as cephalosporins. In this study, we aimed to evaluate antibiotic practices in relation to hospitalized patients with acute abdomen. Methodology This retrospective quality assurance study was conducted among patients admitted to the surgical emergency department at the North Denmark Regional Hospital during a four-month observation period. Data were extracted from electronic patient journals and entered in the Research Electronic Data Capture data management system for further analytical work. Results Of 331 patients, 174 (53%) were treated with antibiotics, of whom 98 (56%) had been treated with cephalosporin, 47 (27%) with benzylpenicillin and gentamicin, 22 (13%) with piperacillin/tazobactam, and seven (4%) with ciprofloxacin. Use of a cephalosporin-based antibiotic regimen was significantly more common in patients with acute appendicitis (75%) compared to other diagnostic groups, such as acute cholecystitis (57%), incarcerated hernia with strangulation (56%), acute pancreatitis (50%), and acute diverticulitis (30%). However, patients with uncomplicated diverticulitis (53%) were significantly more often treated with benzylpenicillin and gentamicin, whereas patients with complicated diverticulitis Hinchey stage 3-4 were significantly more often treated with piperacillin/tazobactam. In addition, as the severity of acute cholecystitis increased, it was more frequently treated with piperacillin/tazobactam. Conclusions The study revealed that cephalosporins are frequently used in patients hospitalized with acute abdomen. This finding conflicts with current regional antibiotic guidelines. Reinforcement of the guidelines is required as an essential measure against the development of antibiotic resistance associated with the use of cephalosporins.

Clinical explainable machine learning models for early identification of patients at risk of hospital-acquired urinary tract infection.

BACKGROUND: Machine learning (ML) models for early identification of patients at risk of hospital-acquired urinary tract infections (HA-UTI) may enable timely and targeted preventive and therapeutic strategies. However, clinicians are often challenged in the interpretation of the predictive outcomes provided by the ML models, which often reach different performances. AIM: To train ML models for predicting patients at risk of HA-UTI using available data from electronic health records at the time of hospital admission. We focused on the performance of different ML models and clinical explainability. METHODS: This retrospective study investigated patient data representing 138.560 hospital admissions in the North Denmark Region from 01.01.2017 to 31.12.2018. We extracted 51 health socio-demographic and clinical features in a full dataset and used the χ2 test in addition to expert knowledge for feature selection, resulting in two reduced datasets. Seven different ML models were trained and compared between the three datasets. We applied the SHapley Additive exPlanation (SHAP) method to support population- and patient-level explainability. FINDINGS: The best-performing ML model was a neural network based on the full dataset, reaching an area under the curve (AUC) of 0.758. The neural network was also the best-performing ML model based on the reduced datasets, reaching an AUC of 0.746. Clinical explainability was demonstrated with a SHAP summary- and forceplot. CONCLUSION: Within 24h of hospital admission, the ML models were able to identify patients at risk of developing HA-UTI, providing new opportunities to develop efficient strategies for the prevention of HA-UTI. Using SHAP, we demonstrate how risk predictions can be explained at individual patient level and for the patient population in general.

Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study.

BACKGROUND: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP. METHODS: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analysed. RESULTS: Among 826 eligible patients ≥18 years old, 529 (64%) were included for data analysis at first follow-up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60 ± 15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<0.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intention-to-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis. CONCLUSION: Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids. SIGNIFICANCE: The findings in this retrospective study conducted in a real-world clinical setting suggest a favourable safety profile of cannabinoids. Moreover, one-sixth (intention-to-treat) and one-third (per-protocol) of patients with chronic pain refractory to conventional analgesics, or experiencing intolerable adverse effects, benefited significantly from therapy with oral cannabinoid regimens. Combination of THC and CBD seems overall more effective than cannabinoid monotherapy. Conduction of randomized controlled trials investigating safety and efficacy of cannabinoid therapy to diagnosis specific patient subgroups with comparable clinical and pathophysiological chronic pain characteristics is warranted, hence contributing further to the process of clinical evidence clarification currently in progress.