René dePont Christensen

Point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind, randomised controlled trial

BACKGROUND When used with standard diagnostic testing, point-of-care ultrasonography might improve the proportion of patients admitted with respiratory symptoms who are correctly diagnosed 4 h after admission to the emergency department. We therefore assessed point-of-care ultrasonography of the heart, lungs, and deep veins in addition to the usual initial diagnostic testing in this patient population. METHODS In a prospective, parallel-group trial in the emergency department at Odense University Hospital, Odense, Denmark, patients (≥18 years) with a respiratory rate of more than 20 per min, oxygen saturation of less than 95%, oxygen therapy, dyspnoea, cough, or chest pain were randomly assigned in a 1:1 ratio with a computer-generated list to a standard diagnostic strategy (control group) or to standard diagnostic tests supplemented with point-of-care ultrasonography of the heart, lungs, and deep veins (point-of-care ultrasonography group). The primary endpoint was the percentage of patients with a correct presumptive diagnosis 4 h after admission to the emergency department. Only the physicians doing the primary clinical assessment and the auditors were masked. Analyses were by intention to treat. The study is registered with ClinicalTrials.gov, number NCT01486394. FINDINGS Between Dec 7, 2011, and March 15, 2013, 320 patients were randomly assigned to the control group (n=160) and point-of-care ultrasonography group (n=160). 158 patients in the point-of-care ultrasonography group and 157 in the control group were analysed. 4 h after admission to the emergency department, 139 patients (88·0%; 95% CI 82·8-93·1) in the point-of-care ultrasonography group versus 100 (63·7%; 56·1-71·3) in the control group had correct presumptive diagnoses (p<0·0001). The absolute and relative effects were 24·3% (95% CI 15·0-33·1) and 1·38 (1·01-1·31), respectively. No adverse events were reported. INTERPRETATION Point-of-care ultrasonography is a feasible, radiation free, diagnostic test, which alongside standard diagnostic tests is superior to standard diagnostic tests alone for establishing a correct diagnosis within 4 h. It should therefore be considered for routine use as part of the standard diagnostic tests in the emergency department for patients admitted with respiratory symptoms. FUNDING University of Southern Denmark, Odense University Hospital, and Højbjerg Fund.

Long-term treatment with probiotics in primary care patients with irritable bowel syndrome – a randomised, double-blind, placebo controlled trial

Abstract Objective. Meta-analyses have indicated effect of probiotics on irritable bowel syndrome (IBS). However, few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting. We aimed to investigate the effect of probiotics compared with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up. Material and methods. We randomized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp paracasei F19, Lactobacillus acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 × 1010 CFU per capsule. Primary endpoint was proportion of responders defined as patients reporting adequate relief (AR) at least 50% of the time in the 6-month treatment period. Secondary outcomes were proportions of patients reporting AR at different time points, and change in gastrointestinal symptoms and health-related quality of life (HrQOL) from baseline to 6 and 12 months. Results. A total of 131 patients were included in this study. The proportion of responders in the treatment period was 52% (35/67) in the probiotic group versus 41% (26/64) in the placebo group, p = 0.18. Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment. Patients improved in HrQOL, but with no statistically significant difference between the groups. Conclusion. During a 6-month treatment period, we were not able to detect a positive effect of probiotic when compared with placebo.

Long term use of drugs affecting the renin-angiotensin system and the risk of cancer: a population-based case-control study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • A recent meta-analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers. WHAT THIS STUDY ADDS • Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin-angiotensin system and users of other antihypertensives. • No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors. AIMS A recent meta-analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose-response and dose-duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs. METHODS We identified 149 417 incident cancer cases in Denmark during the period 2000-2005. Four controls, matched by age and gender, were selected for each case by a risk-set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression. RESULTS The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β-adrenoceptor blockers, thiazide diuretics and α-adrenoceptor blockers. No consistent dose-duration or dose-response association could be demonstrated for ARBs or ACEIs. CONCLUSIONS The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB-cancer association is probably too weak to be addressed in observational studies, given their limitations.

Reproducibility of serum protein profiling by systematic assessment using solid-phase extraction and matrix-assisted laser desorption/ionization mass spectrometry.

Protein profiling of human serum by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) is potentially a new diagnostic tool for early detection of human diseases, including cancer. Sample preparation is a key issue in MALDI MS and the analysis of complex samples such as serum requires optimized, reproducible methods for handling and deposition of protein samples. Data acquisition in MALDI MS is also a critical issue, since heterogeneity of sample deposits leads to attenuation of ion signals in MALDI MS. In order to improve the robustness and reproducibility of MALDI MS for serum protein profiling we investigated a range of sample preparation techniques and developed a statistical method based on repeated analyses for evaluation of protein-profiling performance of MALDI MS. Two different solid-phase extraction (SPE) methods were investigated, namely custom-made microcolumns and commercially available magnetic beads. Using these two methods, nineteen different sample preparation methods for serum profiling by MALDI MS were systematically tested with regard to matrix selection, stationary phase, selectivity, and reproducibility. Microcolumns were tested with regard to chromatographic properties; reversed phase (C8, C18, SDB-XC), ion-exchange (anion, weak cation, mixed-phase (SDB-RPS)) and magnetic beads were tested with regard to chromatographic properties; reversed phase (C8) or affinity chromatography (Cu-IMAC). The reproducibility of each sample preparation method was determined by enumeration and analysis of protein signals that were detected in at least six out of nine spectra obtained by three triplicate analyses of one serum sample.A candidate for best overall performance as evaluated by the number of peaks generated and the reproducibility of mass spectra was found among the tested methods. Up to 418 reproducible peaks were detected in one cancer serum sample. These protein peaks can be part of a possible diagnostic profile, suggesting that this sample preparation method and data acquisition approach is suitable for large-scale analysis of serum samples for protein profiling.

Unmet needs in cancer rehabilitation during the early cancer trajectory – a nationwide patient survey

Abstract Background. A cancer diagnosis may lead to psychosocial problems and physical symptoms that can be relieved during rehabilitation. The aim of this study was to analyse patient-perceived unmet needs of rehabilitation close to time of diagnosis, i.e. frequencies of unmet needs and the association with sociodemographic characteristics, cancer type and treatment. Material and methods. All adult residents of Denmark diagnosed with cancer for the first time from 1 May to 31 August 2010 were mailed a patient questionnaire two to five months following diagnosis. The study population was identified by use of national administrative registers. Data on rehabilitation, family situation, education, and cancer treatment were obtained from the questionnaire, while sex, birth year and cancer type were obtained from the Danish National Patient Registry. The association between each type of unmet needs and the variables sex, age, cancer diagnosis, treatment, education, cohabitation status, and children (living at home and away from home) was analysed using multiple logistic regression. Results. Among the 4346 participants (64.7%) unmet needs were reported with regard to talking to patients in the same situation (24.1%), counselling with a psychologist (21.4%), physical rehabilitation (18.8%), practical help (17.3%), and counselling related to work or education (14.8%). Differences were observed with regard to type of unmet needs, sociodemographic and clinical characteristics, but generally, young age, male sex, low educational level and living alone increased the adjusted odds ratios of unmet needs. Breast cancer and to some extent melanoma cancer decreased the odds. Conclusion. Unmet needs of rehabilitation are frequent during the early cancer trajectory and sociodemographic and clinical inequalities exist. The results support guideline recommendations of integration of cancer rehabilitation from the beginning of the cancer trajectory. Early interventions tailored to men, patients with low educational level, living alone, or treated with chemotherapy may help counterbalancing social and clinical inequalities in the long run.

Survival after stage IA endometrial cancer; can follow-up be altered? A prospective nationwide Danish survey.

Objective. To present Danish national survival data on women with early stage endometrial cancer and use these data to discuss the relevance of postoperative follow‐up. Design. Prospective study. Setting. Danish Endometrial Cancer Study (DEMCA). Population. Five hundred and seventy‐one FIGO stage IA (1988 classification) endometrial cancer patients prospectively included between 1986 and 1999. All patients had total abdominal hysterectomy and bilateral salpingo‐oophorectomy without adjuvant therapy. Methods. The patient and the disease characteristics were drawn from the DEMCA database with cross‐references to the national death registry and the national pathology database. Statistical methods included Kaplan–Meier, log‐rank and Cox regression analysis. Main outcome measures. Survival rates in relation to histopathology. Results. The five year overall survival rate was 88.9% and five year disease‐specific survival was 97.3%. Patients with low‐ (91.8%) and high‐risk histopathology (8.2%) were compared. The age‐adjusted overall and disease‐specific survival differed significantly between women with low‐ and high‐risk histopathology (p = 0.039 and p = 0.004, respectively). The disease‐specific survival adjusted for age between patients with well‐differentiated endometrioid tumors differed from those with moderately differentiated tumors (p = 0.008, hazard ratio = 3.75, 95% confidence interval 1.41–10.00). Recurrence data were available on 464 patients. Twenty‐three (3.9%) experienced recurrence. Of these recurrences, 15 of 23 (65%) were vaginal. Death from recurrence was observed in nine of 23 (39%) patients, and five of these nine had vaginal recurrences. Conclusions. Women with FIGO stage IA endometrial cancer have a very high disease‐specific five year survival. Survival was related to histopathology. Follow‐up at a highly specialized tertiary care center for patients with an extremely good prognosis may be questioned.

Prevalence of overweight and obesity in Danish preschool children over a 10-year period. A study of two birth cohorts in general practice

Aim:  To determine change in the prevalence of overweight and obesity in preschool children, over a 10‐year period and to identify possible predictors of overweight in 5‐year‐old children.

Medical and non-medical predictors of initiating long-term use of proton pump inhibitors: a nationwide cohort study of first-time users during a 10-year period

Studies of the increasing use of proton pump inhibitors (PPIs) have mainly focused on prevalent long‐term use and associations with gastrointestinal morbidity and comedication. Little is known about non‐medical characteristics of first‐time users of PPI, and predictors of initiating long‐term use of PPIs.

Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO)

BackgroundWe evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.MethodsWe performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients.ResultsRecruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated.ConclusionTreatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients.Trial registrationTrial identification number (Clinical Trials.gov): NCT01965080.Nordic Society of Gynecological Oncology: NSGO–EC–0302.EudraCT number: 2004-001103-35.

Treatment of acute otitis media in general practice: quality variations across countries

BACKGROUND Recommendations for antibiotic treatment of acute otitis media (AOM) have changed over the years, and today many experts recommend initial observation. However, antibiotic prescribing should be considered in children aged <2 years or if AOM is accompanied by discharging ear. OBJECTIVES To investigate the quality of treatment of AOM in general practice and to explore the influence of selected GP and patient characteristics on antibiotic prescribing. METHODS During the winter 2008, a prospective registration of patients diagnosed with AOM was conducted in general practice in Lithuania, Kaliningrad, Spain, Argentina, Sweden and Denmark. Some 1175 patients diagnosed with AOM were registered. Information about age and sex of the patient, duration of symptoms (days), temperature >38.5°C, ear discharge and the antibiotic treatment given was recorded. RESULTS Danish GPs had the lowest antibiotic prescription rate for AOM [72.7% (95% confidence interval (CI) = 67.0-77.8)] and GPs in Kaliningrad had the highest [97.1% (95% CI = 89.8-99.6)]. Narrow-spectrum penicillin was almost exclusively prescribed in the two Nordic countries, while broad-spectrum penicillins, often in combination with clavulanic acid, were prescribed in the other four countries. Macrolides comprised 5-10% of prescriptions. Antibiotic prescribing was associated with the following characteristics of the patients: symptoms for >3 days, ear discharge and fever. CONCLUSION The majority of patients with AOM were treated with antibiotics in all six countries, but considerable variations in both prescribing rate and choice of antibiotics were identified.