Deaths Among Ambulance Patients Released from the Emergency Department Within the First 24 Hours With Nonspecific Diagnoses - Expected or Not?

BACKGROUND: Emergency patients are frequently assigned nonspecific diagnoses. Nonspecific diagnoses describe observations or symptoms and are found in chapters R and Z of the International Classification of Diseases, 10th edition (ICD-10). Patients with such diagnoses have relatively low mortality, but due to patient volume, the absolute number of deaths is substantial. However, information on cause of short-term mortality is limited. OBJECTIVES: To investigate whether death could be expected for ambulance patients brought to the emergency department (ED) after a 1-1-2 call, released with a nonspecific ICD-10 diagnosis within 24 h, and who subsequently died within 30 days. METHODS: Retrospective medical record review of adult 1-1-2 emergency ambulance patients brought to an ED in the North Denmark Region during 2017-2021. Patients were divided into three categories: unexpected death, expected death (terminal illness), and miscellaneous. Charlson Comorbidity Index (CCI) was assessed. RESULTS: We included 492 patients. Mortality was distributed as follows: Unexpected death 59.2% (n = 291), expected death (terminal illness) 25.8% (n = 127), and miscellaneous 15.0% (n = 74). Patients who died unexpectedly were old (median age of 82 years) and had CCI 1-2 (58.1%); 43.0% used at least five daily prescription drugs, and they were severely acutely ill upon arrival (24.7% with red triage, 60.1% died within 24 h). CONCLUSIONS: More than half of ambulance patients released within 24 h from the ED with nonspecific diagnoses, and who subsequently died within 30 days, died unexpectedly. One-fourth died from a pre-existing terminal illness. Patients dying unexpectedly were old, treated with polypharmacy, and often life-threateningly sick at arrival.

Are patients with eosinophilic esophagitis treated at an academic hospital comparable to a patient from a population-based cohort? Not in Denmark.

Background and Aim: Little are known about differences in eosinophilic esophagitis (EoE) patients in the general population compared with patients treated at academic hospitals. This might affect the generalizability of study results. The aims of the study were to compare clinical features, and complications of EoE between patients from a population-based cohort (DanEoE) and patients from an academic hospital cohort in Copenhagen (EoE-Cph). Methods: The DanEoE cohort is a population- and register-based cohort including all 236 adult EoE patients diagnosed in the North Denmark Region in 2007-2017 previously described in detail. The new EoE-Cph cohort consists of 245 consecutively referred adult patients to a dedicated EoE center in an Academic Hospital in the Danish capital in 2013-2020. Data were collected from medical registries and medical files. Results: Patients in the academic cohort were at symptom debut 12 (SD 16) years younger (P = 0.001). At the time of diagnosis they were 5.4 (SD 15) years younger (P < 0.001). Where Gastro-esophageal reflux disease (GORD) was present in one-third of the population-based cohort, this was only observed in 14% of the EoE-Cph group (P < 0.05). Food bolus obstruction before diagnosis was 24% less common in the EoE-Cph patients (P < 0.001). Conclusion: Results indicated that EoE patients referred to a Danish EoE center is a selected subgroup with disease debut at a younger age, less comorbid GORD, and rarely food bolus obstruction before diagnosis. This suggests that study results from academic hospitals might not have generalizability to the average EoE patient in a population.

The phenotype of adults with complicated eosinophilic esophagitis is dominated by a 5-year longer diagnostic delay: A population-based study of the DanEoE cohort.

Background and Aim: The DanEoE is a previously described population- and register-based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well-defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. Methods: A retrospective cross-sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. Results: At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis. Conclusion: In the population-based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5-year longer diagnostic delay. In the current study, the complication status did not predict the treatment response.

Efficacy of FODMAP Elimination and Subsequent Blinded Placebo-Controlled Provocations in a Randomised Controlled Study in Patients with Ulcerative Colitis in Remission and Symptoms of Irritable Bowel Syndrome: A Feasibility Study.

Background: Patients with inflammatory bowel disease (IBD) and symptoms of irritable bowel syndrome (IBS) may be intolerant to fermentable carbohydrates (FODMAPs). The aim of this study was to test the feasibility of eliminating and subsequently reintroducing FODMAPs in patients with IBS symptoms as part of the IBD manifestation and to compare the severity of IBS symptoms and pain, bloating and quality of life (QoL). Methods: An eight-week randomised open-label FODMAP elimination with double-blinded, crossover provocations of FODMAP and placebo. Diet patients were on a low-FODMAP diet for eight weeks with blinded two-week provocations after two and six weeks. Questionnaires, blood and stool samples were collected. Results: Patient enrolment was challenging. Nineteen participants were included in the study. Eliminating low FODMAP for two weeks resulted in significant decreases in pain and bloating scores (p < 0.003), whereas there were no statistical differences in pain scores between diet patients and controls. Pain and bloating scores increased, returning to baseline levels after two weeks of double-blinded provocations with placebo, (p > 0.05). Conclusions: The results document the possibility of performing a randomised controlled study following the gold standard for testing food intolerance with blinding of the Low FODMAP diet. Recruitment of participants was challenging.

Acute colonic pseudo-obstruction after cesarean section and gastrointestinal symptoms⋆.

OBJECTIVE: To investigate whether women who developed acute colonic pseudo-obstruction (ACPO) after cesarean section have a higher degree of gastro-intestinal symptoms than women who did not develop ACPO after cesarean section. ACPO is a colonic dilatation without mechanical obstruction, and with an unknown pathophysiology. In younger people it is mostly seen in women after cesarean section. The hypothesis of the present study is that long-term consequences of gastrointestinal symptoms evolve after ACPO, due to the impact on the colon. STUDY DESIGN: 40 women who developed ACPO after cesarean section (cases) and 80 women, who did not develop ACPO after cesarean section (controls), were asked to participate in the study. The controls were matched based on time of cesarean section (± 14 days), age (±5 years), singleton or twin, parity, cesarean section grade, and ASA-group. Baseline characteristics and information regarding the cesarean section were collected from medical records. An electronic collection of surveys was distributed to the participants, including the following: Irritable Bowel Syndrome - Severity Scoring System (IBS-SSS), Rome IV, Gastrointestinal Symptoms Rating Scale (GSRS), Visceral Sensitivity Index (VSI), Patient Health Questionnaire 15 (PHQ15), The MOS 36-item Short-Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). The score from IBS-SSS after cesarean section was used as the primary outcome. RESULTS: 25 cases and 37 controls participated in the study. A difference in blood loss was found with a median of 600 mL in cases, compared to 400 mL in controls during cesarean section (p = 0.002). No difference was found between cases and controls in the IBS-SSS score after cesarean section. However, cases yielded a higher difference between IBS-SSS before and after cesarean section, indicating a higher degree of deterioration in gastrointestinal symptoms (p = 0.026). In addition, cases reported a higher degree of pain in everyday life (p = 0.039). No difference was found in the remaining surveys. CONCLUSION: Women undergoing cesarean section developed mild grade of irritable bowel syndrome. However, gastrointestinal symptoms did not seem to be more prevalent in women who developed ACPO, although women with ACPO had a higher degree of deterioration in gastrointestinal symptoms than controls.

Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett's Esophagus Than in Healthy Controls.

BACKGROUND/AIMS: Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett's esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett's esophagus to that in healthy controls. METHODS: A total of 26 patients with histology-confirmed Barrett's esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. RESULTS: Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pH-measurement and acid clearance test were not correlated (all P > 0.3). CONCLUSIONS: More frequent swallowing and thus faster acid clearance in Barrett's esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes.

The Short Health Scale: A Simple, Valid, Reliable, and Responsive Way of Measuring Subjective Health in Patients With Irritable Bowel Syndrome.

GOALS: To evaluate validity, reliability, and responsiveness of the Short Health Scale (SHS) in irritable bowel syndrome (IBS) patients. BACKGROUND: Subjective health assessment is central when treating patients with IBS. The "Short Health Scale" is a quick 4-item questionnaire covering most aspects of subjective health that has been validated for inflammatory bowel disease. STUDY: To test validity, 451 patients with IBS (mean age, 38 y; 81% females) completed the SHS and questionnaires assessing IBS symptom severity (IBS-SSS), gastrointestinal (GI)-specific anxiety (VSI), and quality of life (IBSQOL). To evaluate reliability and responsiveness to changes, the questionnaires were repeated after 2 weeks in 18 patients, and after 12 weeks in 212 patients who had completed a patient-education program. RESULTS: Validity was documented with (1) gradually increasing mean scores for all 4 SHS items with increasing IBS-SSS (P<0.0001), and (2) correlations between the 4 SHS items and the corresponding items from the other subjective health assessment tools [item 1 (symptom burden): ρ=0.67, item 2 (daily function): ρ=-0.44 to -0.46, item 3 (disease-related worry): ρ=-0.51 to 0.57, item 4 (general well-being): ρ=-0.34 to -0.46, P<0.0001]. Reliability was confirmed (Spearman ρ>0.7 and intraclass correlations >0.7). Responsiveness was good with responders to the patient-education program (IBS-SSS reduction ≥50 points) having significant reductions in 3 of the SHS items (P<0.05), and borderline change for the fourth SHS item (P=0.06). CONCLUSIONS: SHS is a health measure that shows promising evidence of validity, reliability, and responsiveness in IBS patients. It is quickly completed and evaluated, which supports its usefulness in the busy clinical practice.

Is electrical brain activity a reliable biomarker for opioid analgesia in the gut?

The effects of morphine on brain potentials after experimental gut pain have never been investigated. This study explored whether multi-channel-evoked brain potentials (EP) and corresponding dipole sources in the brain would reflect the effects of morphine on experimental oesophageal pain. In a crossover study, the effects of oral morphine (30 mg) or corresponding placebo on pain from electrical oesophageal stimulation were tested in 12 healthy male volunteers. The electroencephalographic (EEG) activity was monitored with 64 surface recordings. Pain was assessed by subjective scores on a visual analogue scale, amplitude and latency of the vertex-EP as well as on multi-channel recordings of EPs. Finally, electrical brain sources after pain stimuli were modelled from the EEG data. Morphine attenuated subjective pain scores (p = 0.008). The amplitude of the P2 peak (230 msec. post-stimulus) in the vertex EPs was unaltered after treatment with morphine, whereas after placebo treatment, it decreased (p = 0.03). However, the overall topography changed and the source of P1 (100 msec. post-stimulus), possibly originating from areas near the cingulate gyrus, changed localization in an upward, posterior direction (p = 0.04). The length of the vector describing this shift correlated inversely with the magnitude of the subjective pain relief (r = -0.7; p = 0.02). With the potential of becoming a useful biomarker in analgesic trials, the localization of the dipole sources reflected the analgesic action of morphine after pain stimuli of the gut. Even though further evaluation of the method is necessary, it has the potential to be a valid objective biomarker for opioid analgesia.

Proximal and distal esophageal sensitivity is decreased in patients with Barrett's esophagus.

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett's esophagus (BE). METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, and evoked brain potentials were recorded. RESULTS: Patients were hyposensitive to heat stimulation both in the metaplastic part [median stimulation time to reach the pain detection threshold: 15 (12-34) s vs 14 (6-23) s in controls; F = 4.5, P = 0.04] and the normal part of the esophagus [median 17 (6-32) s vs 13 (8-20) s in controls; F = 6.2, P = 0.02]. Furthermore, patients were hyposensitive in the metaplastic part of the esophagus to mechanical distension [median volume at moderate pain: 50 (20-50) mL vs 33 (13-50) mL in controls; F = 5.7, P = 0.02]. No indication of central nervous system abnormalities was present, as responses were comparable between groups to electrical pain stimuli in the metaplastic part [median current evoking moderate pain: 13 (6-26) mA vs 12 (9-24) mA in controls; F = 0.1, P = 0.7], and in the normal part of the esophagus [median current evoking moderate pain: 9 (6-16) mA, vs 11 (5-11) mA in controls; F = 3.4, P = 0.07]. Furthermore, no differences were seen for the referred pain areas (P-values all > 0.3) or latencies and amplitudes for the evoked brain potentials (P-values all > 0.1). CONCLUSION: Patients with BE are hyposensitive both in the metaplastic and normal part of esophagus likely as a result of abnormalities affecting peripheral nerve pathways.

The esophageal multimodal pain model: normal values and degree of sensitization in healthy young male volunteers.

BACKGROUND: Sensory changes are thought to be involved in gastro-esophageal reflux disease (GERD). The esophageal multimodal pain model can be used to investigate sensations in response to distension, heat, electric current and acid. AIMS: The aim of this study was to provide normal values for this model in the normal state and in the acid induced sensitized state. METHODS: Fifty-three healthy men (20-38 years old) underwent esophageal stimulation with distension, heat and electrical current before and after sensitization with 0.1 N HCl acid. Stimulus intensities at painful and non-painful thresholds and referred pain areas were measured. The percentage of individual participants sensitized to each modality was calculated. In 22 subjects the pre-acid tests were repeated on three subsequent visits. RESULTS: To reach moderate pain, subjects tolerated mean distension of 29.1 ± 11 mL, heat stimulation time of 141 ± 33 s, and mean current of 17.6 ± 6.4 mA. After acid exposure, significantly reduced thresholds were observed for mechanical (24%), heat (11%) and electrical (14%) stimulation (P values < 0.05). The percentage of subjects sensitized, defined as reductions in thresholds of ≥10% or ≥20% after acid perfusion, was as follows: for distension 77%/62%, for heat 48%/28%, and for current 58%/44%. The model showed good reliability (intra-class correlations >0.6). CONCLUSIONS: Normal values for healthy young men are now provided for the normal and the sensitized state. The percentage of subjects sensitized after acid stimulation are thoroughly documented, and depends on stimulation type and the cut-off value chosen.

Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis.

OBJECTIVES: To gain more information of the pain mechanisms in chronic pancreatitis we applied standardized experimental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. METHODS: Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with 'single and repeated burst' electrical stimuli reflecting activation of peripheral and central pain mechanisms. RESULTS: The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P=0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P=0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P=0.02). CONCLUSIONS: Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients.