Primary care clinicians treat patients with medically unexplained symptoms

OBJECTIVE: There is no proven primary care treatment for patients with medically unexplained symptoms (MUS). We hypothesized that a long-term, multidimensional intervention by primary care providers would improve MUS patients' mental health. DESIGN: Clinical trial. SETTING: HMO in Lansing, MI. PARTICIPANTS: Patients from 18 to 65 years old with 2 consecutive years of high utilization were identified as having MUS by a reliable chart rating procedure; 206 subjects were randomized and 200 completed the study. INTERVENTION: From May 2000 to January 2003, 4 primary care clinicians deployed a 12-month intervention consisting of cognitive-behavioral, pharmacological, and other treatment modalities. A behaviorally defined patient-centered method was used by clinicians to facilitate this treatment and the provider-patient relationship. MAIN OUTCOME MEASURE: The primary endpoint was an improvement from baseline to 12 months of 4 or more points on the Mental Component Summary of the SF-36. RESULTS: Two hundred patients averaged 13.6 visits for the year preceding study. The average age was 47.7 years and 79.1% were females. Using intent to treat, 48 treatment and 34 control patients improved (odds ratio [OR]=1.92, 95% confidence interval [CI]: 1.08 to 3.40; P=.02). The relative benefit (relative "risk" for improving) was 1.47 (CI: 1.05 to 2.07), and the number needed to treat was 6.4 (95% CI: 0.89 to 11.89). The following baseline measures predicted improvement: severe mental dysfunction (P<.001), severe body pain (P=.039), nonsevere physical dysfunction (P=.003), and at least 16 years of education (P=.022); c-statistic=0.75. CONCLUSION: The first multidimensional intervention by primary care clinicians led to clinically significant improvement in MUS patients.     

Differential responses to cannabis potency: a typology of users based on self-reported consumption behaviour

AimsTo determine whether a classification of cannabis users into different types can help to clarify the relationship between cannabis potency and consumption behaviour, harmful physical effects and psychological dependency.MethodsA field sample of 388 respondents was recruited who had smoked cannabis at least once in the past month. They were contacted and interviewed in 28 cannabis coffeeshops located in five Dutch cities. Data were collected with an assisted self-completion questionnaire. Cluster analysis was performed using the k-means method.FindingsVarious ways were observed in which cannabis users in natural settings adjusted their intake to the potency of the drug. Cluster analysis identified three broad types of cannabis users. The strongest high type was the youngest, consumed the highest monthly dose, inhaled higher-potency cannabis more deeply, and scored highest on psychological cannabis dependency. The consistent high type preferred milder cannabis, consumed the lowest monthly dose, and compensated for stronger cannabis by inhaling less deeply and smoking less. The steady quantity type was the oldest, usually smoked alone, consumed an intermediate monthly dose, and did not tend to adjust the depth of inhalation to the potency of the cannabis. The results suggest that this typology might also reflect three successive stages in the careers of continuing cannabis users.ConclusionsLaboratory studies to assess the effects of higher THC concentrations on external and internal exposure to cannabis should allow for the possibility that the types of users studied can affect the results.     

Brain systems mediating semantic and syntactic processing in deaf native signers: Biological invariance and modality specificity

Studies of written and spoken language suggest that nonidentical brain networks support semantic and syntactic processing. Event-related brain potential (ERP) studies of spoken and written languages show that semantic anomalies elicit a posterior bilateral N400, whereas syntactic anomalies elicit a left anterior negativity, followed by a broadly distributed late positivity. The present study assessed whether these ERP indicators index the activity of language systems specific for the processing of aural-oral language or if they index neural systems underlying any natural language, including sign language. The syntax of a signed language is mediated through space. Thus the question arises of whether the comprehension of a signed language requires neural systems specific for this kind of code. Deaf native users of American Sign Language (ASL) were presented signed sentences that were either correct or that contained either a semantic or a syntactic error (1 of 2 types of verb agreement errors). ASL sentences were presented at the natural rate of signing, while the electroencephalogram was recorded. As predicted on the basis of earlier studies, an N400 was elicited by semantic violations. In addition, signed syntactic violations elicited an early frontal negativity and a later posterior positivity. Crucially, the distribution of the anterior negativity varied as a function of the type of syntactic violation, suggesting a unique involvement of spatial processing in signed syntax. Together, these findings suggest that biological constraints and experience shape the development of neural systems important for language.     

Presence of a novel DNA methylation enzyme in methicillin-resistant Staphylococcus aureus isolates associated with pig farming leads to uninterpretable results in standard pulsed-field gel electrophoresis analysis

Genomic DNA from methicillin-resistant Staphylococcus aureus isolates recovered from pigs and their caretakers proved resistant to SmaI digestion, leading to uninterpretable results in standard pulsed-field gel electrophoresis. This is the result of a yet unknown restriction/methylation system in the genus Staphylococcus with the recognition sequence CCNGG.     

Activation and anergy in bone marrow B cells of a novel immunoglobulin transgenic mouse that is both hapten specific and autoreactive

Available evidence indicates that B cell tolerance is attained by receptor editing, anergy, or clonal deletion. Here, we describe a p-azophenylarsonate (Ars)-specific immunoglobulin transgenic mouse in which B cells become anergic as a consequence of cross-reaction with autoantigen in the bone marrow. Developing bone marrow B cells show no evidence of receptor editing but transiently upregulate activation markers and appear to undergo accelerated development. Mature B cells are present in normal numbers but are refractory to BCR-mediated induction of calcium mobilization, tyrosine phosphorylation, and antibody responses. Activation marker expression and acquisition of the anergic phenotype is prevented in bone marrow cultures by monovalent hapten. In this model, it appears that induction of anergy in B cells can be prevented by monovalent hapten competing with autoantigen for the binding site.     

Eribulin Monotherapy in Patients Aged 70 Years and Older With Metastatic Breast Cancer

Purpose.

Following the demonstrated efficacy and safety of eribulin mesylate in heavily pretreated patients with metastatic breast cancer, an exploratory analysis was performed to investigate the effect of age in these patients.

Methods.

Data were pooled from two single-arm phase II studies and one open-label randomized phase III study in which patients received eribulin mesylate at 1.4 mg/m² as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day cycle. The effect of age on median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and incidence of adverse events (AEs) was calculated for four age groups (<50 years, 50–59 years, 60–69 years, ≥70 years).

Results.

Overall, 827 patients were included in the analysis (<50 years, n = 253; 50–59 years, n = 289; 60–69 years, n = 206; ≥70 years, n = 79). Age had no significant impact on OS (11.8 months, 12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5 months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and 21.5%, respectively). Although some AEs had higher incidence in either the youngest or the oldest subgroup, there was no overall effect of age on the incidence of AEs (including neuropathy, neutropenia, and leukopenia).

Conclusion.

Eribulin monotherapy in these selected older patients with good baseline performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of younger patients with metastatic breast cancer. The benefits and risks of eribulin appear to be similar across age groups.     

Role of the coagulation system in allergic inflammation in the upper airways

Thrombin has been detected and demonstrated to play a role in the airways of patients with bronchial asthma, but its role in the upper airways including during allergic rhinitis is unknown. This study was conducted to explore whether thrombin is presence in the upper airways and, if so, whether it affects mucin secretion. Fifteen patients with allergic rhinitis were enrolled in the clinical study; primary nasal septum epithelial cells and normal bronchial epithelial cells were used for in vitro evaluation, and rats as animal models. Significant concentrations of thrombin were found in nasal secretion after allergic provocation in allergic patients, and thrombin and its agonistic receptor peptide induced significant secretion of mucin in primary nasal cells and normal bronchial epithelial cells as compared to non-stimulated cells. Increased mucosubstance secretion in septum epithelial cells was also induced after nasal instillation of thrombin in rats. Further, the anticoagulant, activated protein C, significantly inhibited thrombin-induced mucin secretion from septum epithelial cells in rats. The results of this study suggest that activation of the coagulation system occurs during the allergic response and that thrombin plays a crucial role in the regulation of mucin production in the upper airways.     

Scalp cooling for chemotherapy-induced alopecia

Alopecia is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects. To prevent alopecia scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands. The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs. In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced alopecia.     

Assessing the value of CAN-gene mutations using MALDI-TOF MS

Purpose

To identify cancer-linked genes, Sjöblom et al. and Wood et al. performed a genome-wide mutation screening in human breast and colorectal cancers. 140 CAN-genes were found in breast cancer, which in turn contained overall 334 mutations. These mutations could prove useful for diagnostic and therapeutic purposes.

Methods

We used a MALDI-TOF MS 40-plex assay for testing 40 loci within 21 high-ranking breast cancer CAN-genes. To confirm mutations, we performed single-plex assays and sequencing.

Results

In general, the mutation rate of the analyzed loci in our sample cohort was very low. No mutation from the 40 loci analyzed could be found in the 6 cell lines. In tissue samples, a single breast cancer tissue sample showed heterozygosity at locus c.5834G>A within the ZFYVE26 gene (Zinc finger FYVE domain-containing gene 26).

Conclusions

Sjöblom et al./Wood et al. already showed that the vast majority of CAN-genes are mutated at very low frequency. Due to the fact that we only found one mutation in our cohort, we therefore assume that at the selected loci, mutations might be low-frequency events and therefore, more rarely detectable. However, further evaluation of the CAN-gene mutations in larger cohorts should be the aim of further studies.