Socioeconomic inequalities in prognostic markers of non-Hodgkin lymphoma: analysis of a national clinical database

The survival of non-Hodgkin lymphoma patients strongly depends on a range of prognostic factors. This registry-based clinical cohort study investigates the relation between socioeconomic position and prognostic markers in 6234 persons included in a national clinical database in 2000-2008, Denmark. Several measures of individual socioeconomic position were achieved from Statistics Denmark. The risk of being diagnosed with advanced disease, as expressed by the six prognostic markers (Ann Arbor stage III or IV, more than one extranodal lesion, elevated serum lactate dehydrogenase (LDH), performance status of two or more, presence of B symptoms and International Prognostic Index (IPI) of two or more), increased with decreasing level of education, in patients living alone, and in men. For instance, a significant decrease in the odds of being diagnosed with elevated LDH (p = 0.02), high performance status (p = 0.004), high IPI score (p = 0.004) and B symptoms (p = 0.02) was seen with higher level of education, whereas high stage of disease was significantly less likely in the higher educated (odds ratio [OR] = 0.85 (0.74-0.99)). The difference in risk seemed not to be mediated by differences in histological subgroups reflecting aggressiveness of disease among the social groups. One of the most likely mechanisms of the social difference is longer delay in those with low socioeconomic position. The findings of social inequality in prognostic markers in non-Hodgkin lymphoma (NHL) patients could already be implemented in the clinical practice if general practitioners (GP’s) and physicians on hospitals paid special attention to patients with low educational level and unspecific symptoms.     

Reprint of “Treatment of cannabis use disorders in people with schizophrenia spectrum disorders — A systematic review”

Background

Cannabis use disorders (CUD) are prevalent among people with schizophrenia spectrum disorders (SSD), with a range of detrimental effects, e.g. reduced compliance to medication and psychosocial interventions, and increased level of psychotic-dimension symptoms. The aim of this study was to review literature on treatments of CUD in SSD-patients.

Methods

PubMed, PsycINFO, EMBASE, and The Cochrane Central Register of Controlled Trials were searched.

Results

41 articles were selected, 11 treating cannabis as a separate outcome. Contingency management was only effective while active. Pharmacological interventions appeared effective, but lacked randomized controlled trials (RCTs). Psychosocial interventions, e.g. motivational interviewing and cognitive behavior therapy (CBT), were ineffective in most studies with cannabis as a separate outcome, but effective in studies that grouped cannabis together with other substance use disorders.

Conclusions

Insufficient evidence exists on treating this form of dual-diagnosis patients. Studies grouping several types of substances as a single outcome may overlook differential effects. Future RCTs should investigate combinations of psychosocial, pharmacological, and contingency management.     

Do childhood and adult socioeconomic circumstances influence health and physical function in middle-age?

This study examines the joint and separate contribution of social class in early and adult life to differences in health and physical function in middle-aged men. We use data from the Metropolit project which includes men born in 1953 in Copenhagen and a study of middle-aged Danish twins (MADT). In total 6292 Metropolit participants in a follow-up survey on health in 2004 were included in the study together with 2198 male twins of which 1294 were part of a male twin pair (N = 647 pairs). Logistic regression was used to investigate the association between social class in early and adult life, respectively and health in midlife, measured as limitations in running 100 m, poor dental status, poor self-rated health, and fatigue. In both datasets, men with low childhood or adult social class had a higher risk of being unable to run 100 m, having poor dental status, having poor self-rated health and fatigue than men from the highest social classes. When childhood and adult social class were mutually adjusted, the estimates for both measures were attenuated. Adjustment for living without a partner, body mass index (BMI) and smoking in midlife, which were also related to the four outcomes, had marginal effects on the estimates for childhood social class, but attenuated the effect of adult social class somewhat. Among male twin pairs discordant on adult social class, the twin in the lowest class seemed to be unable to run 100 m, rate own health poorer and being fatigued more often than the high class co-twin, while there seemed to be no twin pair difference in dental status. This suggests that the associations of adult social class with functional limitations, poor self-rated health and fatigue may partly be due to causal effects related to adult social class exposures, while social class differences in dental status might be consistent with an effect of factors mainly operating early in life.     

Effectiveness,safety, and patient reported outcomes of a planned investment procedure in higher-risk chronic total occlusion percutaneous coronary intervention: Rationale and design of the invest-CTO study

Background

The anatomical complexity of a chronic total occlusion (CTO) correlates with procedural failure and complication rates. CTO modification after unsuccessful crossing has been associated with subsequent higher technical success rates, but complication rates remain high with this approach. While successful CTO percutaneous coronary intervention (PCI) has been associated with improved angina and quality of life (QOL) this has not been demonstrated in anatomically high-risk CTOs. Whether a planned CTO modification procedure, hereafter named Investment procedure, could improve patient outcomes has never been investigated.

Study Design

Invest-CTO is a prospective, single-arm, international, multicenter study, evaluating the effectiveness and safety of a planned investment procedure, with a subsequent completion CTO PCI (at 8–12 weeks), in anatomically high-risk CTOs. We will enroll 200 patients with CTOs defined as high-risk according to our Invest CTO criteria at centers in Norway and United Kingdom. Patients with aorto-ostial lesions, occlusion within a previous stent, or a prior attempt at target vessel CTO PCI within 6 months will be excluded. The co-primary endpoints are cumulative procedural success (%) after both procedures, and a composite safety endpoint at 30 days after completion CTO PCI. Patient reported outcomes (PROs), treatment satisfaction, and clinical endpoints will be reported.

Conclusion

This study will prospectively evaluate the effectiveness and safety of a planned two staged PCI procedure in the treatment of high-risk CTOs and may have the potential to change current clinical practice.     

Associations between physical and mental health problems and sexual dysfunctions in sexually active Danes

IntroductionStudies have shown a high prevalence of sexual dysfunctions among individuals with a variety of health problems.AimTo obtain a population‐based assessment of these matters, we studied associations between indicators of physical and mental health problems and sexual dysfunctions in Denmark.MethodsWe used questionnaire data from 4,415 sexually active men (mean age 48 years) and women (mean age 45 years) who participated in a nationally representative survey in 2005. Cross‐sectional associations of overall health and physical and mental health problems with sexual dysfunctions in the last year were estimated by logistic regression‐derived, confounder‐adjusted odds ratios (OR_adj).Main Outcome MeasuresWe calculated OR_adj with 95% confidence intervals (CI) for erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men, for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women, and for sexual dysfunction and sexual difficulties overall in both sexes.ResultsSexual dysfunction was significantly more common among participants with poor self‐rated health (OR_adj 1.86, 95% CI 1.05‐3.33 in men, OR_adj 1.91, 1.08–3.37 in women). Physical health problems were significantly associated with male sexual dysfunctions (OR_adj 1.75, 1.18–2.61), whereas mental health problems were significantly associated with female sexual dysfunctions (OR_adj 2.59, 1.60–4.22).ConclusionAmong sexually active Danes, poor self‐reported overall health is associated with increased rates of sexual dysfunction in both sexes, with physical health problems mainly affecting men's sex lives, and mental health problems being strongly associated with female sexual dysfunction. Christensen BS, Grønbæk M, Osler M, Pedersen BV, Graugaard C, and Frisch M. Associations between physical and mental health problems and sexual dysfunctions in sexually active Danes. J Sex Med 2011;8:1890–1902.     

Balanced translocation in a patient with severe myoclonic epilepsy of infancy disrupts the sodium channel gene SCN1A

In a patient with severe myoclonic epilepsy of infancy (SMEI), we identified a de novo balanced translocation, t(2;5)(q24.3,q34). The breakpoint on chromosome 2q24.3 truncated the SCN1A gene and the 5q34 breakpoint was within a highly conserved genomic region. Point mutations or microdeletions of SCN1A have previously been identified in SMEI patients, but this is the first report of a balanced translocation disrupting the SCN1A gene in an epilepsy patient. We therefore recommend that SMEI patients without SCN1A microdeletions or point mutations should be investigated for chromosomal rearrangements.     

Ex vivo and in vivo delivery of anti-tissue factor short interfering RNA inhibits mouse pulmonary metastasis of B16 melanoma cells.

PURPOSE: The coagulation trigger tissue factor has been implicated in tumor growth, angiogenesis, and metastasis. In this study, we explore the effects of ex vivo and in vivo delivery of short interfering RNA (siRNA) targeting tissue factor on B16 melanoma colonization of the lung in a murine model for metastasis. The purposes of this work are to establish a noncytotoxic in vivo model for investigation of tissue factor function and provide preclinical assessment of the therapeutic potential of tissue factor siRNA for prevention of metastasis. EXPERIMENTAL DESIGN AND RESULTS: C57BL/6 mice were evaluated for pulmonary metastases following tail vein injection of B16 cells transfected with either active or inactive siRNA. Mice receiving cells transfected with active siRNA had significantly lower numbers of pulmonary tumors compared with mice injected with control cells (transfected with inactive siRNA). The average time point at which the mice started to exhibit tumor-associated stress was also increased significantly from 22 days for the control group to 27 days for the experimental group (P = 0.01). In a therapeutically more relevant model, where the siRNA was delivered i.p. and the cells (untransfected) by tail vein injection, an inhibitory effect on metastasis was observed when the siRNA treatment was initiated either before or at the time of cell injection. CONCLUSIONS: The results suggest that tissue factor has a crucial function in promoting lung tumor metastasis of blood-borne tumor cells in the early stages of the tumor take process and further suggest that treatment with tissue factor siRNA may become a viable clinical strategy for prevention of tumor metastasis.