An analysis of the level of evidence behind treatments recommended by the Danish Medicines Council.

OBJECTIVES: We aimed to investigate the quality of evidence and the expected added clinical value of treatments recommended by the Danish Medicines Council (DMC). STUDY DESIGN: This was an observational study. METHODS: The DMC prepares reports on drugs considered for possible new standard treatments in Danish hospitals. These reports evaluate the available evidence on efficacy and safety. The quality of evidence is systematically rated by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria, and estimates of added clinical value are presented. The recommendations take into account expected economic implications of new treatments. The publicly available reports up until December 29, 2021, were downloaded from the DMC Web page. Reports on drugs marked "recommended" were included. Data on quality of evidence, expected clinical value, and economic implications were imputed in a Microsoft Excel spreadsheet. RESULTS: Seventy-nine reports were included in the analysis. In 79% of these, the quality of evidence was rated low (24%) or very low (55%), whereas no recommendations were based on evidence rated as high quality. Three (5%) of recommended treatments were expected to add large clinical value. CONCLUSIONS: Most recommendations by the DMC are based on evidence formally rated as low or very low quality by GRADE, and no recommendations were based on evidence rated as high quality. The added clinical value of the treatments was often not documented and rarely large. Continued attention to improve the clinical evidence behind national recommendations is necessary.

Changes in Body Composition in Older Adults after a Technology-Based Weight Loss Intervention.

We conducted a post-hoc analysis of a pre/post, single-arm, non-randomized, multicomponent weight loss intervention in older adults. Fifty-three older adults aged ≥65 with a body mass index ≥ 30 kg/m2 were recruited to participate in a six-month, remote monitoring and video-conferencing delivered, prescriptive intervention consisting of individual and group-led registered dietitian nutrition and physical therapy sessions. We assessed weight, height, and body composition using a SECA 514 bioelectrical impedance analyzer. Mean age was 72.9±3.9 years (70% female) and all had ≥2 chronic conditions. Of those with complete data (n=30), we observed a 4.6±3.5kg loss in weight, 6.1±14.3kg (1.9%) loss in fat mass, and 0.78±1.69L loss in visceral fat (all p<0.05). Fat-free mass (-3.4kg±6.8, p=0.19), appendicular lean mass (-0.25±1.83, p=0.22), and grip strength (+3.46±7.89, p=0.56) did not significantly change. These variables were preserved after stratifying by 5% weight loss. Our intervention led to significant body and visceral fat loss while maintaining fat-free and appendicular lean muscle mass.

Reported Weight Change in Older Adults and Presence of Frailty.

OBJECTIVE: A 5% change in weight is a significant predictor for frailty and obesity. We ascertained how self-reported weight change over the lifespan impacts rates of frailty in older adults. METHODS: We identified 4,984 subjects ≥60 years with body composition measures from the National Health and Nutrition Examination Survey. An adapted version of Fried's frailty criteria was used as the primary outcome. Self-reported weight was assessed at time current,1 and 10 years earlier and at age 25. Weight changes between each time point were categorized as ≥ 5%, ≤5% or neutral. Logistic regression assessed the impact of weight change on the outcome of frailty. RESULTS: Among 4,984 participants, 56.5% were female, mean age was 71.1 years, and mean BMI was 28.2kg/m2. A weight loss of ≥ 5% had a higher association with frailty compared to current weight, age 25 (OR 2.94 [1.72,5.02]), 10 years ago (OR 1.68 [1.05,2.69]), and 1 year ago (OR 1.55 [1.02,2.36]). Weight gain in the last year was associated with increased rate of frailty (1.59 [1.09,2.32]). CONCLUSION: There is an association between frailty and reported weight loss over time while only weight gain in the last year has an association with frailty.

Development and Usability Assessment of a Connected Resistance Exercise Band Application for Strength-Monitoring.

Resistance exercise bands are a core component of any physical activity strengthening program. Strength training can mitigate the development of sarcopenia, the loss of muscle mass or strength and function with aging. Yet, the adherence of such behavioral exercise strategies in a home-based setting are fraught with issues of monitoring and compliance. Our group developed a Bluetooth-enabled resistance exercise band capable of transmitting data to an open-source platform. In this work, we developed an application to capture this information in real-time, and conducted three usability studies in two mixed-aged groups of participants (n=6 each) and a group of older adults with obesity participating in a weight-loss intervention (n=20). The system was favorable, acceptable and provided iterative information that could assist in future deployment on ubiquitous platforms. Our formative work provides the foundation to deliver home-based monitoring interventions in a high-risk, older adult population.

Usability testing of a prototype Phone Oximeter with healthcare providers in high- and low-medical resource environments.

To increase the use of pulse oximetry by capitalise on the wide availability of mobile phones, we have designed, developed and evaluated a prototype pulse oximeter interfaced to a mobile phone. Usability of this Phone Oximeter was tested as part of a rapid prototyping process. Phase 1 of the study (20 subjects) was performed in Canada. Users performed 23 tasks, while thinking aloud. Time for completion of tasks and analysis of user response to a mobile phone usability questionnaire were used to evaluate usability. Five interface improvements were made to the prototype before evaluation in Phase 2 (15 subjects) in Uganda. The lack of previous pulse oximetry experience and mobile phone use increased median (IQR [range]) time taken to perform tasks from 219 (160-247 [118-274]) s in Phase 1 to 228 (151-501 [111-2661]) s in Phase 2. User feedback was positive and overall usability high (Phase 1--82%, Phase 2--78%).

Right and left cardiac function in HIV-infected patients investigated using radionuclide ventriculography and brain natriuretic peptide: a 5-year follow-up study.

OBJECTIVE: The aim of the study was to determine the incidence of myocardial dysfunction in an HIV-infected population receiving state-of-the-art treatment. METHODS: Between April 2001 and July 2002, 91 HIV-infected patients had a radionuclide ventriculography performed with determination of right ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF), as well as measurement of brain natriuretic peptide (BNP). Between July 2005 and January 2007, 63 patients (69%) agreed to participate in a follow-up study with a mean follow-up of 4.5 years. RESULTS: All patients had normal LVEF at both examinations. A minimal increase in mean LVEF of 0.02 was observed at follow-up (P=0.01). At the initial visit, four patients [6%; 95% confidence interval (CI) 2-15%] had a reduced RVEF, and at follow-up two patients (3%; 95% CI 0-11%) had slightly reduced RVEF. No significant change in mean RVEF was found. No patients had increased BNP and no change in mean plasma BNP was found. CONCLUSIONS: HIV-related cardiomyopathy appears not to constitute a problem in closely monitored, well-treated HIV-infected patients. Compared with pre-highly active antiretroviral therapy (HAART) studies, it seems that the improvement in immunocompetency and viral load has removed the problem of HIV-related cardiomyopathy. Although HAART has been suggested as a possible new cause of cardiomyopathy, we did not find any evidence of this.

Effect of eight weeks of endurance exercise training on right and left ventricular volume and mass in untrained obese subjects: a longitudinal MRI study.

The aim of the present investigation was to examine how 8 weeks of intense endurance training influenced right and left ventricular volumes and mass in obese untrained subjects. Ten overweight subjects (19-47 years; body mass index of 34+/-5 kg/m(2)) underwent intensive endurance training (rowing) three times 30 min/week for 8 weeks at a relative intensity of 72+/-8% of their maximal heart rate response (mean+/-SD). Before and after 8 weeks of endurance training, the left and the right end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), stroke volume (SV) and ventricular mass (VM) were measured by Magnetic resonance imaging (MRI). Submaximal heart rate decreased from 126+/-5 to 113+/-3 b.p.m. (10%; P<0.01), and from 155+/-5 to 141+/-4 b.p.m. (9%; P<0.001) at submaximal workloads of 70 and 140 W (110 W for women), respectively (mean+/-SEM). Resting ventricular parameters increased significantly: left ventricular SV, EDV and VM increased by 6%, 7% and 13%, respectively (P<0.01). The right side of the heart showed significant changes in SV, EDV and VM with increase of 4%, 4% and 12%, respectively (P<0.05). Eight weeks of endurance training significantly increased left ventricular SV and right ventricular SV, due to an increase in left ventricular EDV and right ventricular EDV. Furthermore, left VM and right VM increased. We conclude that using MRI and a longitudinal design it was possible to demonstrate similar and balanced changes in the right and left ventricle in response to training.

Evaluation of left ventricular mass measured by 3D echocardiography using magnetic resonance imaging as gold standard.

OBJECTIVE: Increased left ventricular mass (LVM) and presence of left ventricular hypertrophy (LVH) are predictors of cardiovascular morbidity and mortality, but can be reversed with proper treatment of the underlying cause. Therefore accurate as well as reproducible methods for diagnosis and follow-up are needed. We evaluated different modalities by which to measure LVM in patients with no known LVH using magnetic resonance imaging (MRI) as the gold standard: ECG using the formulae proposed by Sokolow-Lyon and Cornell, 2D echocardiography and 3D echocardiography. METHODS: 34 subjects were included in the study; 17 had a history of myocardial infarction, 7 had pulmonary hypertension and 10 were healthy. All patients and controls had a standard 12-lead ECG, a transthoracic 2D and 3D echocardiographic study and a cardiac MRI. RESULTS: ECG estimates of LVM correlated poorly with LVM by MRI (r = 0.18, NS and 0.16, NS for Sokolow-Lyon and Cornell, respectively), whereas a moderate correlation between 2D and 3D echocardiography and MRI was observed (r = 0.63, p<0.001 and r = 0.74, p<0.001, respectively). All methods were reproducible with no significant bias. CONCLUSION: LVM measured by 3D echocardiography is highly accurate compared to LVM measured by MRI. LVM calculated from 2D echocardiography also proved useful, whereas estimates of LVM by ECG are inaccurate in a non-hypertrophic population.

Comparison between two artificial shelter units and timed manual collections for detecting peridomestic Triatoma infestans (Hemiptera: Reduviidae) in rural northwestern Argentina.

A new artificial shelter unit was compared with segments of bamboo cane lined with pleated filter paper for detecting peridomestic Triatoma infestans Klug at Amamá and nearby rural villages in northwestern Argentina. The new shelter unit consisted of a black plastic, wide-mouthed jar with a screw cap on the top, and a removable central structure made of pleated corrugated paper. In devices exposed from February to December 1999 at 24 sites positive for T. infestans by timed manual collections with an irritant in April 1999, the cumulative percentage of sites with any sign of infestation detected by the shelter unit increased from 71% after 2 mo to 96% after 10 mo, whereas bamboo cane units concurrently detected only 12-42% of the sites. Sensitivity increased with time of exposure and the abundance of T. infestans per site. In 19 sites negative for T. infestans by inspection, shelters increasingly detected infestation at 16-63% of sites after 10 mo, whereas the bamboo canes only detected one infestation. Shelter units inspected three times over an 11-mo period were significantly more sensitive than a single manual search with an irritant performed in March 2000. Our study provided conclusive field evidence that the shelter unit was more sensitive for detecting peridomestic T. infestans than were timed manual searches, the standard reference method, or bamboo cane units. Rapid timed searches by skilled bug collectors during the early surveillance phase overlooked many peridomestic populations that, in the absence of control, inevitably would increase in abundance and repopulate treated areas.

Serial changes in atrial natriuretic peptide and endothelin-1 concentrations. Their relationships to the cardiac performance of patients hospitalized for acute myocardial infarction.

AIM: The study was designed to assess temporal changes in atrial natriuretic peptide (ANP) and endothelin-1 (ET) concentrations in patients hospitalized for acute myocardial infarction (AMI) and their relationships to cardiac performance determined by radionuclide ventriculography. PATIENTS AND METHODS: 20 patients with first AMI were studied. Blood samples were drawn within the first 4-18 h, after 18-24 h, and on days 2, 3 and 6. Plasma concentrations of ANP and ET were measured in blood samples taken simultaneously. Radionuclide ventriculography was performed on the day of discharge to determine left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic volume index, end-systolic volume index and left-ventricular stroke volume index. RESULTS: Median concentrations of ET decreased from 2.15 pmol/l on admission to 1.45 pmol/l at discharge (32%, p < 0.001). Median ANP rose from 29 to 79 pg/ml (172%, p < 0.001). The increment in ANP and the decrease in ET concentrations from admission to discharge was inversely correlated (r = -0.81, p < 0.005). ANP was inversely correlated to LVEF (r = -0.82, p < 0.001) and to the end-systolic volume index at discharge (r = -0.73, p < 0.003). CONCLUSION: Dynamic and inverse fluctuations in ET and ANP occur within the 1st week of AMI. The magnitude of endocrine activation in the ANP-ET system seems to reflect an impairment in the left-ventricular systolic performance.

Reliability of the Modified Ashworth Scale in the assessment of plantarflexor muscle spasticity in patients with traumatic brain injury.

Although the Modified Ashworth Scale (MAS) is commonly used to assess the severity of muscle spasticity for ankle plantarflexors, its reliability has only been established for elbow muscles. Interrater reliability, intrarater reliability and temporal (between-days) reliability were examined in this study. Also, interrater reliability for use of the scale with plantarflexors was compared with reported results from the measurement of elbow flexors. Thirty adult volunteers with traumatic brain injuries participated. There were 20 men and 10 women; the mean age was 28.3 years (SD = 10.8). Two physical therapists used the MAS to score the subjects independently. Measurements were repeated to yield multiple scores for intrarater reliability assessment. Twenty-one of the subjects returned individually on separate days to be measured again, so that temporal reliability could be assessed. Spearman's correlation coefficients were 0.73 for interrater reliability 0.74 and 0.55 for intrarater reliability, and 0.82 for temporal reliability. Overall, reliability of the MAS for assessing plantarflexor spasticity in patients with traumatic brain injury was found to be minimally adequate to support its continued use. However, interrater reliability was less than that which has been reported for elbow flexors, and intrarater reliability findings were mixed.

Beta 2-microglobulin expression of AIDS-related and classical Kaposi's sarcoma.

The expression of beta 2-microglobulin, the invariable light chain of HLA class I molecules, of Kaposi's sarcoma from 11 AIDS patients and from 11 patients without known immunodeficiency was studied by immunohistochemistry using a polyclonal antibody to beta 2-microglobulin. The staining intensity of spindle cells in these lesions was scored in a semiquantitative system. We found that the spindle cells of Kaposi's sarcomas from AIDS patients showed significantly increased staining intensity for beta 2-microglobulin compared to those of Kaposi's sarcomas from non-AIDS patients. The results may indicate that Kaposi's sarcomas developing in immunocompromised individuals, such as AIDS patients, are not subject to immune selection by T cells eliminating HLA class I high-expressing tumor cells, while this may be the case in non-AIDS patients. Alternatively, the results may be caused by differences in the activity of cytokines, which upregulate the expression of HLA class I molecules on the cell surface.

[Embolic episodes after treatment of atrial fibrillation in a patient with thyrotoxicosis]. / Emboliske episoder efter behandling af atrieflimren hos en patient med tyreotoksikose.

Thyrotoxic artrial fibrillation is well known and occurs in 10-30% of all patients with thyrotoxicosis. The risk of systemic embolism has been found to be 10-40% in patients with thyrotoxic atrial fibrillation. We present a case of 53 year-old man, a healthy and active athlete, with atrial fibrillation and thyrotoxicosis. He was treated with a beta-blocking agent (sotalol) and sent home. Seven days later, he suffered systemic arterial emboli, one in the right arm and one in the left leg. After embolectomy the patient started anticoagulation and no further complications occurred. Previous studies are discussed, and the following conclusions made. When taken together the data suggest that the rate of embolism in patients with thyrotoxic atrial fibrillation exceeds that of non-thyrotoxic atrial fibrillation unassociated with rheumatic heart disease. The majority of clinically evident embolic events that occur in patients with thyrotoxic atrial fibrillation involve the central nervous system. The rate of embolic events appears to be greatest early in the course of thyrotoxic atrial fibrillation, but may persist for some weeks after conversion and may be particularly high in patients with associated heart failure. It is suggested that anticoagulation therapy should be considered in these patients.

Changes in left and right ventricular performance and volumes in seven-year survivors of acute myocardial infarction.

We describe the spontaneous long-term changes in right (RV) and left (LV) ventricular performance during a 7-year period after acute myocardial infarction (AMI). Radionuclide ventriculography was performed in the second week after AMI in 201 patients. RV and LV ejection fractions, and LV end-diastolic and end-systolic volumes were determined. A follow-up after 7 years was performed in 55 survivors. Of these, 16 patients were also examined after 1 year. During the 7-year follow-up period, LV ejection fraction decreased from 0.49 to 0.45 (p < 0.01). LV end-diastolic volume increased from 161 to 210 ml (30%) (p < 0.01), and LV end-systolic volume from 83 to 123 ml (48%) (p < 0.01). In patients without recurrent AMI, coronary artery bypass grafting surgery, or angiotensin-converting enzyme inhibitor therapy (n = 37) during follow-up, no change in average LV ejection fraction was observed. Nevertheless, this subgroup had substantial increases in LV end-diastolic volume, from 157 to 190 ml (21%) (p = 0.002) and in LV end-systolic volume, from 80 to 105 ml (31%) (p < 0.001). In a subgroup of patients also reinvestigated after 1 year (n = 16), there was a 15% increase in LV end-diastolic volume the first year after AMI with an additional 10% increase in LV end-diastolic volume between years 1 and 7. Corresponding figures for LV end-systolic volume were 20% and 12%, respectively. Hardly any association was apparent between LV ejection fraction, LV end-diastolic volume, and LV stroke volume at discharge for subsequent LV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelin release and enhanced regional myocardial ischemia induced by cold-air inhalation in patients with stable angina.

This study was designed to determine the influence of cold-air inhalation on regional myocardial perfusion in patients with ischemic heart disease. A selected group of vasoactive hormones was measured to investigate their possible roles as ischemic agents. Ten men who had recently had a myocardial infarction and anginal symptoms and with verified pathologic ST deviations during a preceding exercise test volunteered to participate in this randomized cross-over study. Two identical exercise tests were performed on different days; one with inhalation of cold (-22 degrees C) air and the other one with inhalation of thermoneutral air (22 degrees C). Scintigraphic imaging (single-photon emission computed tomography) of regional myocardial blood flow was performed with technetium 99m isonitrile flowtracer and a Bull's eye visual display with calculation of the scintigraphic ischemic severity score. The score was significantly higher during exercise with inhalation of cold air as compared to exercise with inhalation of thermoneutral air. Furthermore, only with cold-air inhalation did arterial plasma endothelin concentration increase significantly from rest to exercise and correlate with the change of ischemic severity score. In contrast, no change was observed under thermoneutral conditions. There was no significant difference between peak values of heart rate, systolic blood pressure, adrenaline, and noradrenaline concentrations in the two situations. We conclude that inhalation of cold air during exercise increases the degree of regional myocardial ischemia and that this is not caused by an increased myocardial oxygen demand. We suggest that cold air directly influences the vasomotor tone of the myocardial resistance vessels and that endothelin may be involved in the ischemic response.

Hormonal and hemodynamic changes following single-dose felodipine treatment during mental stress.

Mental stress induces changes in hemodynamic variables and in the plasma level of many hormones and plasma peptides. These changes can be modulated by various drugs, eg, beta-blockers. In a double-blind, placebo-controlled crossover study, the authors evaluated the hormonal and hemodynamic changes during psychological stress and the effect of felodipine 10 mg (plain tablet). Eight male volunteers participated. Heart rate, blood pressures, and stroke volume were measured by ECG, mercury sphygmomanometer, and impedance cardiography. Catecholamines and atrial natriuretic factor in plasma were measured by electrochemical and radioimmunoassay techniques. A single dose of felodipine, 10 mg, exaggerates the heart rate decreases the left ventricular ejection time and augments the plasma level increment of noradrenaline. The stress-induced changes in other variables were not influenced by felodipine treatment. In conclusion, acute felodipine treatment influences the reflex activation of the sympathetic nervous system during psychological stress. In the treatment of patients, especially patients with heart disease, these findings could be important but further investigations in patients need to be done.

Expression of beta 2-microglobulin by premalignant epithelium.

Many human tumors express low amounts of HLA class I molecules relative to the normal cells from which they are derived. From experimental work it is clear that the malignant behavior of a tumor cell may depend on its MHC class I expression. Therefore, it is of obvious interest to study the HLA class I expression of human tumors in their various stages. We have studied the HLA class I expression by the cells in premalignant epithelial lesions and invasive carcinoma of the bladder and uterine cervix using immunoperoxidase staining for beta 2-microglobulin of paraffin-embedded tissue. We here assume that beta 2-microglobulin expression by malignant and premalignant cells equals HLA class I expression. Thirty-two of the 36 invasive tumors expressed less overall beta 2-microglobulin than cells from the normal epithelium. In contrast, approximately two-thirds of 34 premalignant bladder epithelia and 47 premalignant cervix epithelia displayed higher overall beta 2-microglobulin expression than the normal epithelium. Thus, a systematic large-scale elimination of HLA class I high-expressing tumor cell variants may take place only after the tumor penetrates the basement membrane.