Low-dose ketamine as an adjunct to morphine: A randomized controlled trial among patients with and without current opioid use.

BACKGROUND: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low-dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use. METHODS: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0-10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction. RESULTS: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5-67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3-6]) compared to the placebo group (1 [IQR 0-2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min. CONCLUSIONS: LDK may be effective as an adjunct analgesic to morphine for short-term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use.

As-needed opioid dosing for emergency patients with a daily use of opioids.

BACKGROUND: Patients with a daily use of opioids have a higher risk of insufficient pain treatment during hospitalization than other patients. This study aimed to examine whether as-needed opioid doses (PRN) were adequately adjusted when patients were admitted to the emergency department (ED) with pain. METHODS: Patients, with a daily use of opioids, who received PRN opioid within the first 3 h after admission at the ED at Aarhus University Hospital, Denmark, were prospectively included from February 2021 to June 2021. The primary outcome was the proportion of patients receiving an inadequate initial dose of PRN opioid, here defined as <15% of daily dose of opioids (DDO) based on sparse evidence, but aligning with the prevailing clinical practice. Secondary outcomes included risk of an inadequate PRN dose in relation to DDO (patients were dichotomized into two groups (DDO <60 or ≥60 mg/day). RESULTS: Among 252 patients admitted to the ED with a daily use of opioids, 149 were admitted with pain and 82 received a PRN opioid dose within 3 h. Twenty-seven out of 82 (33%) patients received a PRN dose of <15% of DDO (95% CI: 23.7-43). When dichotomised; 10 out of 50 (20%) patients with a DDO <60 mg/day (95% CI: 10.0-33.7) versus 17 out of 32 (53.1%) patients with a DDO ≥60 mg/day (95% CI: 34.7-70.9) received an inadequate PRN dose (relative risk, RR: 2.65 [95% CI: 1.4-5.1]). CONCLUSIONS: Patients with daily use of opioids presenting in the ED with acute pain had a high risk of inadequate PRN opioid dose, especially if the DDO was high. Awareness about and education focusing on sufficient PRN doses for patients with a daily use of opioids is (still) called for.

Prognostic and discriminative accuracy of the quick Sepsis-related Organ Failure Assessment compared with an early warning score: a Danish cohort study.

BACKGROUND: The clinical benefit of implementing the quick Sepsis-related Organ Failure Assessment (qSOFA) instead of early warning scores (EWS) to screen all hospitalised patients for critical illness has yet to be investigated in a large, multicentre study. METHODS: We conducted a cohort study including all hospitalised patients ≥18 years with EWS recorded at hospitals in the Central Denmark Region during the year 2016. The primary outcome was intensive care unit (ICU) admission and/or death within 2 days following an initial EWS. Prognostic accuracy was examined using sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). Discriminative accuracy was examined by the area under the receiver operating characteristic curve (AUROC). RESULTS: Among 97 332 evaluated patients, 1714 (1.8%) experienced the primary outcome. The qSOFA ≥2 was less sensitive (11.7% (95% CI: 10.2% to 13.3%) vs 25.1% (95% CI: 23.1% to 27.3%)) and more specific (99.3% (95% CI: 99.2% to 99.3%) vs 97.5% (95% CI: 97.4% to 97.6%)) than EWS ≥5. The NPV was similar for the two scores (EWS ≥5, 98.6% (95% CI: 98.6% to 98.7%) and qSOFA ≥2, 98.4% (95% CI: 98.3% to 98.5%)), while the PPV was 15.1% (95% CI: 13.8% to 16.5%) for EWS ≥5 and 22.4% (95% CI: 19.7% to 25.3%) for qSOFA ≥2. The AUROC was 0.72 (95% CI: 0.70 to 0.73) for EWS and 0.66 (95% CI: 0.65 to 0.67) for qSOFA. CONCLUSION: The qSOFA was less sensitive (qSOFA ≥2 vs EWS ≥5) and discriminatively accurate than the EWS for predicting ICU admission and/or death within 2 days after an initial EWS. This study did not support replacing EWS with qSOFA in all hospitalised patients.

Unburdening dementia - a basic social process grounded theory based on a primary care physician survey from 25 countries.

OBJECTIVE: To explore dementia management from a primary care physician perspective. DESIGN: One-page seven-item multiple choice questionnaire; free text space for every item; final narrative question of a dementia case story. Inductive explorative grounded theory analysis. Derived results in cluster analyses. Appropriateness of dementia drugs assessed by tertiary care specialist. SETTING: Twenty-five European General Practice Research Network member countries. SUBJECTS: Four hundred and forty-five key informant primary care physician respondents of which 106 presented 155 case stories. MAIN OUTCOME MEASURES: Processes and typologies of dementia management. Proportion of case stories with drug treatment and treatment according to guidelines. RESULTS: Unburdening dementia - a basic social process - explained physicians' dementia management according to a grounded theory analysis using both qualitative and quantitative data. Unburdening starts with Recognizing the dementia burden by Burden Identification and Burden Assessment followed by Burden Relief. Drugs to relieve the dementia burden were reported for 130 of 155 patients; acetylcholinesterase inhibitors or memantine treatment in 89 of 155 patients - 60% appropriate according to guidelines and 40% outside of guidelines. More Central and Northern primary care physicians were allowed to prescribe, and more were engaged in dementia management than Eastern and Mediterranean physicians according to cluster analyses. Physicians typically identified and assessed the dementia burden and then tried to relieve it, commonly by drug prescriptions, but also by community health and home help services, mentioned in more than half of the case stories. CONCLUSIONS: Primary care physician dementia management was explained by an Unburdening process with the goal to relieve the dementia burden, mainly by drugs often prescribed outside of guideline indications. Implications: Unique data about dementia management by European primary care physicians to inform appropriate stakeholders. Key points Dementia as a syndrome of cognitive and functional decline and behavioural and psychological symptoms causes a tremendous burden on patients, their families, and society. •We found that a basic social process of Unburdening dementia explained dementia management according to case stories and survey comments from primary care physicians in 25 countries. •First, Burden Recognition by Identification and Assessment and then Burden Relief - often by drugs. •Prescribing physicians repeatedly broadened guideline indications for dementia drugs. The more physicians were allowed to prescribe dementia drugs, the more they were responsible for the dementia work-up. Our study provides unique data about dementia management in European primary care for the benefit of national and international stakeholders.

How comorbidities impact Early Warning Score as a predictor of 7-day mortality.

BACKGROUND: Early Warning Score systems are used to monitor patients at risk of deterioration. How comorbidities impact Early Warning Score's ability to predict short-term mortality in the emergency department is not fully elucidated. The aim of the study was to investigate how comorbidities impact Early Warning Score as predictor of 7-day mortality. METHODS: This is an observational cohort study of adult emergency department patients attending one of the five emergency departments in Central Region Denmark from 1 March 2015 to 31 May 2015. Charlson Comorbidity Index was used as a measure of comorbidities. Logistic regression was used to calculate the odds ratio for 7-day mortality. Patients were compared in three groups: Charlson Comorbidity Index: 0, 1-2, 3+. RESULTS: A total of 30 060 adult patients attended one of the five emergency departments. Nineteen thousand one hundred twenty-three patients were included. Charlson Comorbidity Index 3+ patients presenting with Early Warning Score 0, 1-2 or 3-4 had significantly higher odds ratio of 7-day mortality compared to Charlson Comorbidity Index 0 patients with equal Early Warning Score. For patients with Early Warning Score 5+, Charlson Comorbidity Index -status had no significant impact on 7-day mortality after adjusting for age. CONCLUSION: In patients presenting with lower acuity (Early Warning Score 0-4) Charlson Comorbidity Index has a significant impact on 7-day mortality regardless of Early Warning Score. Including Charlson Comorbidity Index status in Early Warning Score or adjusting for Charlson Comorbidity Index -status could increase the predictive value of Early Warning Score in predicting 7-day mortality.

A systematic review and meta-analysis of return to work after mild Traumatic brain injury.

OBJECTIVE: To perform a systematic review and meta-analysis of return to work (RTW) times for adult patients with mild traumatic brain injury (mTBI). METHODS: Six databases and six trials registries were searched. Inclusion: studies reporting RTW, > 30 patients, adults, with mTBI. Exclusion: final measurement RTW < 30 days after injury, first measurement > 1 year. RESULTS: Of 978 records, 14 eligible studies were identified. Two included patients exclusively in paid employment pre-injury; four included paid employment, students, homemakers or other activities; seven included pre-injury occupational status described but unclear; one included patients whose pre-injury occupational status not described. Three reported average RTW, 12 reported proportions of patients RTW at pre-specified time-points (1 both). Average RTW times varied from 13 to 93 days. At 1 month the proportion of patients RTW (three pooled studies) was 0.56 (95% CI 0.30-0.79), at 6 months (six studies) 0.83 (0.74-0.89), at 12 months (seven studies) 0.89 (0.83-0.93). CONCLUSION: More than half of patients with mTBI have returned to work by 1 month after injury, and more than 80% by 6 months. Most studies had poor internal validity. Reporting of outcomes in mTBI is variable, and this accounted for some of the heterogeneity found in this review.

Utilisation of primary care before a childhood cancer diagnosis: do socioeconomic factors matter?: A Danish nationwide population-based matched cohort study.

OBJECTIVES: Early diagnosis of childhood cancer is critical. Nevertheless, little is known about the potential role of inequality. This study aims to describe the use of primary care 2 years before a childhood cancer diagnosis and to investigate whether socioeconomic factors influence the use of consultations and diagnostic tests in primary care. DESIGN: A national population-based matched cohort study. SETTING AND PARTICIPANTS: This study uses observational data from four Danish nationwide registers. All children aged 0-15 diagnosed with cancer during 2008-2015 were included (n=1386). Each case was matched based on gender and age with 10 references (n=13 860). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was additional rates for consultations and for invoiced diagnostic tests for children with cancer according to parental socioeconomic factors. Furthermore, we estimated the association between socioeconomic factors and frequent use of consultations, defined as at least four consultations, and the odds of receiving a diagnostic test within 3 months of diagnosis. RESULTS: Children with cancer from families with high income had 1.46 (95% CI 1.23 to 1.69) additional consultations 3 months before diagnosis, whereas children from families with low income had 1.85 (95% CI 1.60 to 2.11) additional consultations. The highest odds of frequent use of consultations was observed among children from low-income families (OR: 1.94, 95% CI 1.24 to 3.03). A higher odds of receiving an invoiced diagnostic test was seen for children from families with mid-educational level (OR: 1.46, 95% CI 1.09 to 1.95). CONCLUSION: We found a socioeconomic gradient in the use of general practice before a childhood cancer diagnosis. This suggests that social inequalities exist in the pattern of healthcare utilisation in general practice.

Use of general practice before and after mild traumatic brain injury: a nationwide population-based cohort study in Denmark.

OBJECTIVES: Traumatic brain injury (TBI) is commonly seen in the emergency department (ED). Approximately 85%-90% of TBIs are mild (mTBI). Some cause symptoms such as headache, dizziness, anxiety, blurred vision, insomnia and concentration difficulties, collectively known as postconcussion syndrome (PCS). Some studies suggest that recovery from mTBI is complete. Others find that symptoms persist for months, even years. The aim of this study was to describe the use of general practice, before and after mTBI, as a proxy for symptoms in a large cohort. DESIGN: Nationwide population-based matched cohort study. SETTING: Danish EDs and general practice. PARTICIPANTS: All patients (aged ≥18 years), first-time diagnosed with mTBI in a Danish ED between 1 January 1998 and 31 December 2010 (n=93 517). Ten reference persons per patient with mTBI were randomly matched on gender, age and general practice (n=935 170). PRIMARY OUTCOME: Overall use of general practice; consultations relating to mental and physical health. RESULTS: We found higher use of general practice during the first year after mTBI for all ages, both genders and all types of contacts. Age 18-40 years: women, incidence rate ratio (IRR) 1.59 (95% CI 1.57 to 1.61); men, IRR 1.82 (95% CI 1.80 to 1.85). Age 41-65 years: women, IRR 1.75 (95% CI 1.72 to 1.78); men, IRR 1.85(95% CI 1.82 to 1.89). Age 66+ years: women, IRR 1.55 (95% CI 1.52 to 1.58); men, IRR 1.55 (95% CI 1.51 to 1.59). After the first year, the use decreased to the level before mTBI. Individuals with mTBI and higher use of general practice before mTBI had lower socioeconomic status and more comorbidities (P<0.001). CONCLUSIONS: The use of general practice was higher in the first year after mTBI, specifically in the first 3 months. Patients with mTBI had different healthcare-seeking behaviour several years before diagnosis than their matched reference persons. Pretraumatic morbidity should be considered in the evaluation of PCS.

Exploring dementia management attitudes in primary care: a key informant survey to primary care physicians in 25 European countries.

BACKGROUND: Strategies for the involvement of primary care in the management of patients with presumed or diagnosed dementia are heterogeneous across Europe. We wanted to explore attitudes of primary care physicians (PCPs) when managing dementia: (i) the most popular cognitive tests, (ii) who had the right to initiate or continue cholinesterase inhibitor or memantine treatment, and (iii) the relationship between the permissiveness of these rules/guidelines and PCP's approach in the dementia investigations and assessment. METHODS: Key informant survey. SETTING: Primary care practices across 25 European countries. SUBJECTS: Four hundred forty-five PCPs responded to a self-administered questionnaire. Two-step cluster analysis was performed using characteristics of the informants and the responses to the survey. MAIN OUTCOME MEASURES: Two by two contingency tables with odds ratios and 95% confidence intervals were used to assess the association between categorical variables. A multinomial logistic regression model was used to assess the association of multiple variables (age class, gender, and perceived prescription rules) with the PCPs' attitude of "trying to establish a diagnosis of dementia on their own." RESULTS: Discrepancies between rules/guidelines and attitudes to dementia management was found in many countries. There was a strong association between the authorization to prescribe dementia drugs and pursuing dementia diagnostic work-up (odds ratio, 3.45; 95% CI 2.28-5.23). CONCLUSIONS: Differing regulations about who does what in dementia management seemed to affect PCP's engagement in dementia investigations and assessment. PCPs who were allowed to prescribe dementia drugs also claimed higher engagement in dementia work-up than PCPs who were not allowed to prescribe.

Being Young and Getting Cancer: Development of a Questionnaire Reflecting the Needs and Experiences of Adolescents and Young Adults with Cancer.

PURPOSE: Cancer is the leading cause of nonaccidental deaths among adolescents and young adults (AYAs). In Denmark, there are substantial gaps in knowledge concerning how AYAs with cancer perceive their diagnostic and therapeutic trajectory and report health-related outcomes. The aim of this study is to describe the development of a questionnaire targeting AYAs with cancer aiming to evaluate treatment and survivorship from the perspective of the patients. METHODS: Identification of themes and development of items included in the questionnaire were based on a synthesis of literature and qualitative interviews with AYAs in an iterative process involving both a professional advisory panel and a youth panel. During the development process, items were validated through cognitive interviews. RESULTS: The final questionnaire contained 151 closed- and open-ended items divided into 6 sections regarding: (1) "Time before treatment," (2) "Being told about your illness," (3) "Being a young patient," (4) "Your treatment," (5) "Receiving help living with and after Cancer," and (6) "How are you feeling today?." One hundred one items were specifically developed for this study, while 50 were standardized validated indexes. The questionnaire combined different types of items such as needs, preferences, experiences, and patient-reported outcomes. CONCLUSION: This is one of few developed questionnaires aiming to evaluate the perspective of AYAs with cancer through their whole cancer trajectory. Results from the questionnaire survey are intended for quality improvements and research in AYA cancer care. The study highlights the importance of an extensive patient involvement in all steps of a questionnaire development process.

Primary Care Use before Cancer Diagnosis in Adolescents and Young Adults - A Nationwide Register Study.

INTRODUCTION: Survival rates of cancer patients have generally improved in recent years. However, children and older adults seem to have experienced more significant clinical benefits than adolescents and young adults (AYAs). Previous studies suggest a prolonged diagnostic pathway in AYAs, but little is known about their pre-diagnostic healthcare use. This study investigates the use of primary care among AYAs during the two years preceding a cancer diagnosis. METHODS: The study is a retrospective population-based matched cohort study using Danish nationwide registry data. All persons diagnosed with cancer during 2002-2011 in the age group 15-39 years were included (N = 12,306); each participant was matched on gender, age and general practice with 10 randomly selected references (N = 123,060). The use of primary healthcare services (face-to-face contacts, blood tests and psychometric tests) was measured during the two years preceding the diagnosis (index date), and collected data were analysed in a negative binomial regression model. RESULTS: The cases generally increased their use of primary care already from 8 months before a cancer diagnosis, whereas a similar trend was not found for controls. The increase was observed for all cancer types, but it started at different times: 17 months before a diagnosis of CNS tumour, 12 months before a diagnosis of soft tissue sarcoma, 9 months before a diagnosis of lymphoma, 5-6 months before a diagnosis of leukaemia, bone tumour or GCT, and 3 months before a diagnosis of malignant melanoma. CONCLUSION: The use of primary care among AYAs increase several months before a cancer diagnosis. The diagnostic intervals are generally short for malignant melanomas and long for brain tumours. A prolonged diagnostic pathway may indicate non-specific or vague symptomatology and low awareness of cancer among AYAs primary-care personnel. The findings suggest potential of faster cancer diagnosis in AYAs.

Use of primary care during the year before childhood cancer diagnosis: a nationwide population-based matched comparative study.

OBJECTIVE: Childhood cancer is rare and symptoms tend to be unspecific and vague. Using the utilization of health care services as a proxy for symptoms, the present study seeks to determine when early symptoms of childhood cancer are seen in general practice. METHODS: A population-based matched comparative study was conducted using nationwide registry data. As cases, all children in Denmark below 16 years of age (N = 1,278) diagnosed with cancer (Jan 2002-Dec 2008) were included. As controls, 10 children per case matched on gender and date of birth (N = 12,780) were randomly selected. The utilization of primary health care services (daytime contacts, out-of-hours contacts and diagnostic procedures) during the year preceding diagnosis/index date was measured for cases and controls. RESULTS: During the six months before diagnosis, children with cancer used primary care more than the control cohort. This excess use grew consistently and steadily towards the time of diagnosis with an IRR = 3.19 (95%CI: 2.99-3.39) (p<0.0001) during the last three months before diagnosis. Children with Central Nervous System (CNS) tumours had more contacts than other children during the entire study period. The use of practice-based diagnostic tests and the number of out-of-hours contacts began to increase four to five months before cancer diagnosis. CONCLUSIONS: The study shows that excess health care use, a proxy for symptoms of childhood cancer, occurs months before the diagnosis is established. Children with lymphoma, bone tumour or other solid tumours had higher consultation rates than the controls in the last five months before diagnosis, whereas children with CNS tumour had higher consultation rates in all twelve months before diagnosis. More knowledge about early symptoms and the diagnostic pathway for childhood cancer would be clinically relevant.

The 5-minute Apgar score as a predictor of childhood cancer: a population-based cohort study in five million children.

OBJECTIVE: The aetiology of childhood cancer remains largely unknown but recent research indicates that uterine environment plays an important role. We aimed to examine the association between the Apgar score at 5 min after birth and the risk of childhood cancer. DESIGN: Nationwide population-based cohort study. SETTING: Nationwide register data in Denmark and Sweden. STUDY POPULATION: All live-born singletons born in Denmark from 1978 to 2006 (N=1 771 615) and in Sweden from 1973 to 2006 (N=3 319 573). Children were followed up from birth to 14 years of age. MAIN OUTCOME MEASURES: Rates and HRs for all childhood cancers and for specific childhood cancers. RESULTS: A total of 8087 children received a cancer diagnosis (1.6 per 1000). Compared to children with a 5-min Apgar score of 9-10, children with a score of 0-5 had a 46% higher risk of cancer (adjusted HR 1.46, 95% CI 1.15 to 1.89). The potential effect of low Apgar score on overall cancer risk was mostly confined to children diagnosed before 6 months of age. Children with an Apgar score of 0-5 had higher risks for several specific childhood cancers including Wilms' tumour (HR 4.33, 95% CI 2.42 to 7.73). CONCLUSIONS: A low 5 min Apgar score was associated with a higher risk of childhood cancers diagnosed shortly after birth. Our data suggest that environmental factors operating before or during delivery may play a role on the development of several specific childhood cancers.

Presenting symptoms of children with cancer: a primary-care population-based study.

BACKGROUND: Knowledge of how children with cancer present in general practice is sparse. Timely referral from general practice is important to ensure early diagnosis. AIM: To investigate the presenting symptoms and GPs' interpretations of symptoms of children with cancer. DESIGN AND SETTING: A Danish nationwide population-based study including children (<15 years) with an incident cancer diagnosis (January 2007 to December 2010). METHOD: A questionnaire on symptoms and their interpretation was mailed to GPs (n=363). Symptoms were classified according to the International Classification of Primary Care (ICPC)-2 classification. RESULTS: GPs' response rate was 87% (315/363) and GPs were involved in the diagnostic process of 253 (80.3%) children. Symptoms were few (2.4 per child) and most fell into the category 'general and unspecified' (71.9%), apart from patients with tumours of the central nervous system (CNS), whose symptoms fell mostly in the category 'neurological' (for example, headache). Symptoms like pain, swelling/lump, or fatigue were reported in 25% of the patients and they were the most commonly reported symptoms. GPs interpreted children's symptoms as alarm symptoms in 20.2%, as serious (that is, not alarm) symptoms in 52.9%, and as vague symptoms in 26.9%. GPs' interpretation varied significantly by diagnosis (P<0.001). CONCLUSION: Children with cancer presented with few symptoms in general practice, of which most were 'general and unspecified' symptoms. Only 20% presented alarm symptoms, while 27% presented vague and non-specific symptoms. This low level of alarm symptoms may influence the time from symptom presentation in general practice to final diagnosis.

The initial cancer pathway for children - one-fourth wait more than 3 months.

AIM: To determine the time intervals from symptom to treatment for childhood cancer patients. METHODS: Danish national population-based study. Children (<15 years) with an incident cancer diagnosed from January 2007 to December 2010 were sampled. A total of 376 (68%) parents and 315 (87%) general practitioners (GPs) completed questionnaires on the diagnostic pathway. The time interval was categorized into, patient-, GP-, system-, diagnostic- and total intervals, and as short or long intervals. Factors associated with long time intervals were assessed in a logistic regression model using prevalence ratios (PRs). RESULTS: Girls were almost twice as likely as boys to experience long patient intervals (adjusted PR: 1.8, 95% confidence interval (CI): 1.1-2.8). The oldest children were more likely than the youngest to experience long total intervals (adjusted PR: 1.9, 95% CI: 1.1-3.3). Cancer type was associated with all time intervals, except GP intervals. Children with bone- and CNS tumours had the longest total intervals (median: 88 days, interquartile interval (IQI): 57-132) vs. (median: 76, IQI: 28-191). Parental education showed a possible association with patient- and GP intervals. CONCLUSION: Time intervals varied by gender, age and cancer type. Parental education may possibly affect the patient- and GP intervals.