Demographics of HIV-1 infection in Denmark: results from the Danish HIV Cohort Study

We used a population-based cohort study design to describe the demographic characteristics of the HIV-infected population in Denmark and their variation over time. HIV treatment in Denmark is restricted to 9 centres, and all 3941 HIV-1 infected patients more than 15 y old seen at these centres in 1995-2003 were included. We found an estimated HIV prevalence of 70 per 100,000, and a mean annual incidence rate of 5.1 per 100,000 persons. The number of newly infected individuals was stable with a median of 231 per y (period 1995-2002), whereas the number of deaths decreased from 166 in 1995 to 50 in 2000 (p=0.000) and remained stable thereafter. Of the enrolled patients, 75% were males, 80% were Caucasian, 13% were black African, and the primary risk behaviour was male-to-male sexual contact (44%), heterosexual contact (36%), and injection drug use (11%). During the y 1995-2003 we found an increase in age at diagnosis (p=0.000), and no major changes in gender, race, mode of infection, or baseline CD4+ cell count and viral load, neither overall not within subgroups of patients. In this period 14.5% had AIDS at the time of HIV diagnosis. Our data do not confirm concerns about unmonitored evolution in the HIV epidemic in Denmark.     

Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.     

Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.     

Ultrasound appearance and dynamic evaluation of variant long head of the biceps tendon anatomy with MRI correlation

Many variants of the long head of the biceps tendon exist but their appearance has not been documented with ultrasonography (US). We describe a case of variant LHB anatomy that was visualized by magnetic resonance imaging and confirmed with US. Additionally, US was useful to exclude instability of the LHBT. To the best of our knowledge, this variant appearance of the LHBT has not been previously described with US. Considering that shoulder US is routinely performed clinically, knowledge of the appearance of variant LHBT anatomy may be useful.

Electronic supplementary material

The online version of this article (doi:10.1007/s40477-014-0125-2) contains supplementary material, which is available to authorized users.     

Hand‐held Dynamometer Positioning Impacts Discomfort During Quadriceps Strength Testing: A Validity and Reliability Study

Purpose/Background

A belt‐stabilized hand‐held dynamometer (HHD) offers the ability to quantify quadriceps muscle strength in a clinical environment, but a limitation is participant discomfort at the interface between the HHD and the tibia. The purpose of this study was to quantify the level of discomfort associated with a modified belt‐stabilized HHD configuration compared to a standard belt‐stabilized configuration and an isokinetic dynamometer. The secondary purpose of this study was to determine the validity and reliability of a modified configuration used to measure quadriceps strength compared to the “gold‐standard” isokinetic dynamometer.

Methods

Twenty healthy participants (5 males, 15 females; age=24.7±2.2 years, height=171.1±8.8 cm, mass=72.0±18.7 kg) performed maximal knee extension isometric contractions during each of three testing conditions: isokinetic dynamometer, standard configuration with HHD placement on the tibia, and an alternative configuration with the HHD interfaced with the leg of a table. Discomfort was quantified using a Visual Analog Scale (VAS). Differences in discomfort and torque (N•m) associated with the testing positions were determined using Friedman test or repeated measures analysis of variance. Validity was quantified using Pearson correlations and within‐session intrarater reliability was determined using an intraclass correlation coefficient (ICC2,1) and associated confidence intervals (95% CI).

Results

The isokinetic dynamometer configuration resulted in the least discomfort (p< .01) and the modified configuration was more comfortable than the standard configuration (p= .003). There was a significant correlation between measures from the isokinetic dynamometer and the standard configuration (r=.87) and modified configuration (r=.93). Within‐session intrarater reliability was good for both the standard configuration (ICC_2,1=0.93) and modified configuration (ICC_2,1=0.93) conditions.

Conclusions

The use of the modified belt‐stabilized HHD configuration, where the HHD was interfaced with the leg of a table, offers a more comfortable alternative compared to the standard belt‐stabilized configuration to obtain isometric quadriceps strength measures in a clinical environment. This configuration is also a valid and reliable alternative to the “gold standard” isokinetic dynamometer when testing isometric quadriceps strength at 90° of knee flexion.

Level of Evidence

Diagnostic, Level 3     

Randomised study of the influence of non-steroidal anti-inflammatory drugs on the treatment of peptic ulcer in patients with rheumatic disease.

Sixty-seven patients with rheumatic disease, treated with non-steroidal anti-inflammatory drugs (NSAIDs), entered a controlled trial with a diagnosis of duodenal (n = 51), gastric (n = 14), or gastric and duodenal (n = 2) ulcers. The main objectives of the study were a comparison of ranitidine and sucralfate in ulcer treatment, and to observe the influence of continued NSAID administration during peptic ulcer therapy. Ulcers healed within nine weeks in 52 patients. The mean healing time was similar in 27 patients given ranitidine 150 mg bd (4.9 weeks) and 25 patients given sucralfate 1 g qid (4.6 weeks). In patients with unhealed ulcers after nine weeks of treatment, healing was obtained in seven after further therapy for 3-9 weeks. Of the 30 patients who continued NSAIDs during treatment with either ranitidine or sucralfate, 23 ulcers healed (mean healing time: 5.0 weeks). Of 32 patients in whom NSAIDs were stopped, ulcer healing was documented in 29 (mean healing time: 4.6 weeks). The difference in healing rates was not statistically significant (p greater than 0.10). The outcome of ulcer treatment did not differ in patients with rheumatoid arthritis and patients suffering from osteoarthritis. During a 12 month follow up 14 symptomatic ulcer recurrences were recorded.     

One-carbon metabolism markers are associated with cardiometabolic risk factors

Background and aims

Alterations to one-carbon metabolism, especially elevated plasma homocysteine (Hcy), have been suggested to be both a cause and a consequence of the metabolic syndrome (MS). A deeper understanding of the role of other one-carbon metabolites in MS, including s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), and the methylation capacity index (SAM:SAH ratio) is required.

A transgenic model to study the pathogenesis of somatic mtDNA mutation accumulation in β-cells

Low levels of somatic mutations accumulate in mitochondrial DNA (mtDNA) as we age; however, the pathogenic nature of these mutations is unknown. In contrast, mutational loads of >30% of mtDNA are associated with electron transport chain defects that result in mitochondrial diseases such as mitochondrial encephalopathy lactic acidosis and stroke-like episodes. Pancreatic β-cells may be extremely sensitive to the accumulation of mtDNA mutations, as insulin secretion requires the mitochondrial oxidation of glucose to CO₂. Type 2 diabetes arises when β-cells fail to compensate for the increased demand for insulin, and many type 2 diabetics progress to insulin dependence because of a loss of β-cell function or β-cell death. This loss of β-cell function/β-cell death has been attributed to the toxic effects of elevated levels of lipids and glucose resulting in the enhanced production of free radicals in β-cells. mtDNA, localized in close proximity to one of the major cellular sites of free radical production, comprises more than 95% coding sequences such that mutations result in changes in the coding sequence. It has long been known that mtDNA mutations accumulate with age; however, only recently have studies examined the influence of somatic mtDNA mutation accumulation on disease pathogenesis. This article will focus on the effects of low-level somatic mtDNA mutation accumulation on ageing, cardiovascular disease and diabetes.     

Reduced Effectiveness of Interruptive Drug-Drug Interaction Alerts after Conversion to a Commercial Electronic Health Record

Background

Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue.

Objective

To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates.

Design

Two before-and-after studies.

Participants

3277 clinicians who received a DDI alert in the outpatient setting.

Intervention

Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria.

Main Measures

Alert burden and proportion of alerts accepted.

Key Results

Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P?<?0.001). After disabling the least severe alerts, total DDI alert burden fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P?<?0.01).

Conclusions

Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.