Upper respiratory tract infections in general practice: diagnosis,antibiotic prescribing,duration of symptoms and use of diagnostic tests

A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.     

Usefulness of hypertensive blood pressure response during a single-stage exercise test to predict long-term outcome in patients with peripheral arterial disease

The prognostic value of a hypertensive blood pressure (BP) response is still unclear. Therefore, the prognostic value of a hypertensive BP response in patients during single-stage exercise testing for peripheral arterial disease (PAD) on long-term mortality and major adverse cerebrovascular and cardiac events (MACCEs) was investigated. In addition, effects of statin, beta-blocker, and aspirin use in patients with known or suspected PAD were studied. A total of 2,109 patients were enrolled in an observational prospective study from 1993 to 2005. Hypertensive BP response was defined as an increase in systolic BP >/=55 mm Hg (95(th) percentile within our population) after a single-stage treadmill exercise test. The outcome was obtained by using the civil registries, and a questionnaire about cardiac events was sent to all survivals. Hypertensive BP response was associated with increased risk of long-term mortality (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12 to 1.80) and MACCEs (HR 1.47, 95% CI 1.09 to 1.97). After adjustments for clinical risk factors and propensity score, baseline statin use was associated with reduced risk of long-term mortality (HR 0.59, 95% CI 0.44 to 0.79), and statin, beta-blocker, and aspirin use were associated with reduced risk of MACCEs (HR 0.59, 95% CI 0.43 to 0.81; HR 0.75, 95% CI 0.60 to 0.95; HR 0.73, 95% CI, 0.57 to 0.92, respectively). In conclusion, hypertensive BP response at exercise in patients with known or suspected PAD is an important independent risk factor for all-cause long-term mortality and MACCEs, whereas statin, beta-blocker, and aspirin use were associated with an improved outcome.     

Adolescents’ somatic complaints in eight countries: what influence do parental rearing styles have?

Medically unexplained physical symptoms are frequently named by adolescents in both clinical and normative samples. This study analyzed the associations between parental rearing styles and adolescents’ body complaints in diverse cultural contexts. In a cross-cultural study of 2415 adolescents from eight countries (Argentina, France, Germany, Greece, Pakistan, Peru, Poland, and Turkey), the associations of maternal and paternal support, psychological control, and an anxious parental monitoring style with youth body complaints were tested. Girls reported more somatic complaints than boys, the level of complaints differed between countries, and gender differences varied significantly between countries. Hierarchic multilevel models revealed that the expression of distress via body complaints, after controlling for country, gender, and sociodemographic status, was significantly associated with parental rearing styles. The negative impact of mothers’ psychological control on body complaints generalize across countries. In addition, mothers’ anxious monitoring had a negative impact on the offspring’s health, whereas higher levels of paternal support and lower levels of paternal psychological control contributed to lower levels of somatic complaints. Sociodemographic variables such as family structure, standard of living, and employment status of the parents, did not turn out as significant in the final model. The findings point to the different roles of fathers and mothers play in adolescents’ health and their complex interplay.

     

Glutamate Signaling via the AMPAR Subunit GluR4 Regulates Oligodendrocyte Progenitor Cell Migration in the Developing Spinal Cord

Oligodendrocyte progenitor cells (OPCs) are specified from discrete precursor populations during gliogenesis and migrate extensively from their origins, ultimately distributing throughout the brain and spinal cord during early development. Subsequently, a subset of OPCs differentiates into mature oligodendrocytes, which myelinate axons. This process is necessary for efficient neuronal signaling and organism survival. Previous studies have identified several factors that influence OPC development, including excitatory glutamatergic synapses that form between neurons and OPCs during myelination. However, little is known about how glutamate signaling affects OPC migration before myelination. In this study, we use in vivo, time-lapse imaging in zebrafish in conjunction with genetic and pharmacological perturbation to investigate OPC migration and myelination when the GluR4A ionotropic glutamate receptor subunit is disrupted. In our studies, we observed that gria4a mutant embryos and larvae displayed abnormal OPC migration and altered dorsoventral distribution in the spinal cord. Genetic mosaic analysis confirmed that these effects were cell-autonomous, and we identified that voltage-gated calcium channels were downstream of glutamate receptor signaling in OPCs and could rescue the migration and myelination defects we observed when glutamate signaling was perturbed. These results offer new insights into the complex system of neuron-OPC interactions and reveal a cell-autonomous role for glutamatergic signaling in OPCs during neural development.SIGNIFICANCE STATEMENT The migration of oligodendrocyte progenitor cells (OPCs) is an essential process during development that leads to uniform oligodendrocyte distribution and sufficient myelination for central nervous system function. Here, we demonstrate that the AMPA receptor (AMPAR) subunit GluR4A is an important driver of OPC migration and myelination in vivo and that activated voltage-gated calcium channels are downstream of glutamate receptor signaling in mediating this migration.     

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

The IL-1 family member IL-38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL-38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL-38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19⁺ B cells from PBMC was lower, whereas cell-associated IL-38 expression was comparable. In vitro, IL-38 is released from CD19⁺ B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL-38, compared to 100-fold induction of IL-6 and IL-1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL-38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL-38 also correlated inversely with high sensitivity C-reactive protein (p < 0.01), IL-6, IL-1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL-38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL-38 as an anti-inflammatory cytokine.     

Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy Provides Insights into Duplication Mechanisms and Allele‐Specific Expression

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication‐based mechanisms such fork stalling and template switching or microhomology‐mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients’ fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele‐specific LMNB1 expression levels.     

A qualitative participatory study to identify experiences of coronary heart disease patients to support the development of online self-management services

ObjectiveWeb-based self-management services remain underutilized in current practice. Our aim was to gain insight into disease and self-management experiences of patients in early and progressive stages of coronary heart disease (CHD), to understand moderating effects of daily life experiences on the utilization of web-based self-management services and preconditions for use.MethodsWe applied generative research techniques, which stem from the field of product design and are characterized by the use of creative processes. Three groups of patients with CHD received a sensitizing package to document and reflect on their health, and were subsequently either interviewed or participated in a focus group session.ResultsIn total, 23 patients participated in this study. Emerging themes were (1) fear for recurrent events, (2) experiences with professional care, (3) the perceived inability to prevent disease progression, (4) the desire to go on living without thinking about the disease every day, (5) the social environment as a barrier to or facilitator for self-management, and (6) the need for information tailored to personal preferences.ConclusionHow patients experience their disease varies between stable and post-acute stages, as well as between early and progressive stages of CHD. Patients in post-acute stages of the disease seem to be most amenable to support, while patients in stable stages want to live their life without being reminded of their disease. In the context of self-management, web-based services should be adapted to the variation in needs that occur in the different stages of CHD and new strategies to fit such services to these needs should be developed. Furthermore, they should be tailored to patients’ individual health situation and preferences, support patient empowerment, and manage expectations regarding the progression of their disease.