Doctor, what's wrong with me? Factors that delay the diagnosis of colorectal cancer

Objective

To examine the influence of patient and physician communication factors on diagnostic delay (DD).

Methods

242 patients diagnosed with colorectal cancer (CRC) in the past 6 months who experienced symptoms prior to diagnosis were administered a 2-h semi-structured qualitative interview to assess communication with health care provider and ease of access to care, among other factors. Patient-provided information was verified via review of medical records.

Results

The factors associated with DD > 2 months included lower income (OR = 0.56, p = 0.03), having regular physician prior to receiving a cancer diagnosis (OR = 2.52, p = 0.03), having a physician who used temporizing communication strategies during the consultation (OR = 2.41, p = 0.02), receiving an initial alternate diagnosis (OR = 3.36, p = 0.02), experiencing referral delay (OR = 3.61, p = < 0.001), and experiencing follow-up delay of any kind (OR = 3.32, p = 0.01).

Conclusion

Excellent communication skills that appropriately probe for relevant social and economic patient information, assist patients in distinguishing and elaborating on symptoms, and provide clear rationale and instructions for future steps, will speed along the diagnosis process and could be the difference between early and late stage CRC.

Practice implications

Increased understanding of physician communication and practice styles that contribute to DD could have a positive impact on decreasing the morbidity and mortality from this disease.     

Late-onset ADHD in adults: Milder, but still dysfunctional

Objective

The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria - AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients.

Methods

The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models.

Results

Late-onset subjects were diagnosed later (P = 0.04), had a lower frequency of problems with authority and discipline (P = 0.004), and lower scores in SNAP-IV (P < 0.001) and in Barkley’s scale for problems in areas of life activities (P = 0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) (P = 0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics.

Conclusions

This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.     

Material-specific lateralization of working memory in the medial temporal lobe

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging studies, which have focused primarily on visual and visuospatial WM. In the present study we investigated material-specific lateralization of WM in 96 patients with unilateral damage to MTL stemming from TLE (56 left) and 30 control subjects using a pair of matched verbal and visuospatial supraspan tasks. Patients with unilateral TLE were impaired on both verbal and visuospatial WM tasks irrespective of the affected hemisphere. Patients with unilateral right TLE showed an additional deficit for visuospatial WM capacity when contrasted with patients with left TLE, whereas patients with unilateral left TLE showed increased intrusion errors on the verbal task when compared to patients with right TLE. These findings suggest a material-specific lateralization of WM in the MTL.     

Recherche étiologique lors d’un état de mal épileptique

Because of the wide range of etiologies which may provoke status epilepticus (SE), physical examination, laboratory tests and neuroimaging must be conducted according to a well-designed hierarchical system. While implementing intensive care management, clinicians must of course search for curable causes but also consider the possible interaction of multiple factors and hidden diseases favoring or triggering SE. Causes of SE in idiopathic or cryptogenic epilepsy and new-onset SE do not correlate but careful analysis of serum chemistry and neuroimaging abnormalities must nevertheless be conducted with the specific objective of establishing an etiological diagnosis.     

Low serum BDNF and food intake regulation: A possible new explanation of the pathophysiology of eating disorders

Background

Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behavior, and poorly balanced diets lead to a decrease in blood BDNF levels. However, studies regarding BDNF blood levels in eating disorders (ED) have yielded inconsistent results. We measured serum concentrations of BDNF and assessed behavior and cognition related to eating in ED patients and control subjects.

Methods

Forty female drug-free patients [19 with anorexia nervosa (AN), 21 with bulimia nervosa (BN)], who did not meet the diagnostic criteria for depressive disorder, and 24 age-matched normal control subjects were enrolled in the current study. We evaluated eating-related psychopathology and depressive symptoms using the Eating Disorder Inventory-2 (EDI-2), Eating Attitude Test-26 (EAT-26) and the Hamilton Depression Rating Scale (HDRS), and measured serum BDNF levels by an enzyme-linked immunosorbent assay.

Results

Compared to normal controls, serum levels of BDNF were significantly reduced in AN, but not in BN. There was a significant positive correlation between serum BDNF levels and BMI in both AN patients (r = .649, p = .003) and BN patients (r = .626, p = .002). However, no correlation between serum BDNF levels and BMI was detected in the controls. Furthermore, there was a significant negative correlation between serum BDNF levels and the oral control subscale scores of EAT in both AN patients (r = − .506, p = .027) and BN patients (r = − .511, p = .018); whereas, no correlation was detected in normal controls.

Conclusion

Our study demonstrated that individuals showing more extreme food intake regulation were those with lower serum BDNF levels. This finding is contrary to that in mice where mice with reduced BDNF levels showed aberrant eating behavior. This result suggests that BDNF is no longer functioning appropriately in ED patients, which could be an important factor in the pathophysiological of ED.     

Reduced activation in the mirror neuron system during a virtual social cognition task in euthymic bipolar disorder

Social cognition entails both cognitive and affective processing, and impairments in both have accounted for residual symptoms of bipolar disorder (BD). However, there has been a lack of studies identifying neural substrates responsible for social cognitive difficulties in BD patients. Fourteen euthymic BD patients and 14 healthy normal controls underwent functional MRI while performing a virtual reality social cognition task, which incorporated both cognitive and emotional dimensions, simulating real-world social situations. During the scanning, subjects tried to guess (attribute) possible reasons for expressed emotion of virtual humans (avatars) while viewing their facial expressions, just after observing their verbal and nonverbal (facial) expressions which were emotionally valenced (happy, angry and neutral). BD patients compared to normal controls showed delayed reaction times in emotional conditions, with comparable response accuracy. Healthy normal controls activated the right anterior cingulate cortex, inferior frontal, and insular cortex in emotional conditions contrasted with neutral control conditions, that is, the regions that have been related to empathic processes during viewing others' emotional expression. Relative to normal controls, BD patients showed reduced activations in the ‘mirror neuron system’, including the right inferior frontal cortex, premotor cortex, and insula, mainly in angry or happy condition. These results may suggest that, even during euthymic state, BD patients have difficulties in recruiting brain regions for the utilization of emotional cues as a means for understanding others. Clinical attention should be paid to emotion-related residual symptoms to help improve social outcomes in these patients.     

Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology

Exposure to childhood trauma may induce persistent changes in Hypothalamic-Pituitary-Adrenal (HPA)-axis functioning even in the absence of current psychopathology. Because previous studies did not systematically exclude subjects with lifetime psychiatric morbidity, prevalent psychopathology may have confounded the association. In this study we investigated whether women exposed to childhood trauma, but without a history of psychiatric disorders, show alterations in HPA-axis functioning. We included 10 women exposed to significant childhood trauma and 12 non-exposed women. All women were between 29 and 64 years old, mentally and physically healthy, and without current or lifetime psychopathology. HPA-axis functioning was assessed as 1) basal activity with salivary cortisol patterns over 8 time points on two consecutive sampling days and 2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7 time points after the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) challenge test. Basal salivary cortisol output did not differ between trauma-exposed compared to non-exposed women. Significantly blunted plasma cortisol and ACTH responses in response to dex/CRH administration were found in the trauma-exposed compared to the non-exposed women (F(1,20) = 5.08, p = 0.04 and F(1,20) = 5.23, p = 0.03 respectively). Adjusting for age, body mass index (BMI), oral contraceptive use, and menopausal status, somewhat weakened the associations for cortisol as well as ACTH (F(1,16) = 3.30, p = 0.09) and F(1,16) = 2.17, p = 0.16 respectively), but for cortisol absolute differences in point estimates were largely unaffected. Although basal cortisol patterns were similar in the two groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis reactivity in women who were free of current or lifetime psychopathology.     

Association analysis between the C-1291G polymorphism in the promoter region of the adrenergic α2A receptor gene and polydipsia in schizophrenia

Several lines of studies have shown the existence of an important inhibitory mechanism for the control of water intake involving adrenergic α2A receptors (ADRA2A). A human study using patients with schizophrenia demonstrated an exacerbation of polydipsia by the administration of clonidine, an ADRA2A-agonist, and a relief of polydipsia by mianserin, an ADRA2A-antagonist, suggesting the involvement of the central adrenergic system in the drinking behavior of patients with schizophrenia. Based on these findings we examined a possible association between the C-1291G polymorphism in the promoter region of the ADRA2A gene and polydipsia in schizophrenia using a Japanese case-control sample. Our sample includes 348 patients with schizophrenia (DSM-IV) (84 with polydipsia and 264 without polydipsia). No significant association between the ADRA2A C-1291G polymorphism and polydipsia was found. Our result suggests that the ADRA2A C-1291G polymorphism may not confer susceptibility to polydipsia in schizophrenia in our sample. Further studies with larger samples are warranted.     

Do schizophrenia and bipolar disorders share a common disease susceptibility variant at the MMP3 gene?

There is growing evidence of partial etiological overlap between schizophrenia (SZ) and bipolar I disorder (BD-I) from linkage analysis, genetic epidemiology and molecular genetics studies. SZ and BD-I are neurodevelopmental disorders with genetic and environmental etiologies. Recent studies have demonstrated that matrix metalloproteinase 3 (MMP3) is a key event in associative memory formation, learning and synaptic plasticity, which are important in psychiatric disorders. In the light of these findings, we analyzed the genetic variations in the MMP3-1171 5A/6A in patients with SZ, patients with BD-I and healthy controls. To the best of our knowledge, this is the first study to report an association of variation in gene encoding MMP3 with SZ. Our study group consisted of 111 unrelated patients with SZ, 141 unrelated patients with BD-I, and 121 unrelated healthy controls. The frequencies of 6A6A genotype and 6A allele distributions of MMP3 in patients with SZ were significantly decreased when compared with controls. In contrast, in patients with SZ, the distributions of 5A5A genotype and 5A allele of MMP3 gene were significantly increased as compared with healthy controls. When the frequencies of genotypes or alleles in schizophrenic patients and bipolar patients were compared, 6A6A genotype and 6A allele in patients with BD-I were significantly higher than patients with SZ. In contrast, 5A5A genotype and 5A allele distributions of MMP3 gene were significantly frequent in patients with SZ. On the other hand, no significant differences were found in the allele or genotype distribution in patients with BD-I compared with controls. In conclusion, our data have supported the hypothesis that there is a possible relationship between − 1171 5A/6A polymorphism of MMP3 gene and SZ. A larger sample group is needed to confirm the potential role of this gene in the pathophysiology of psychiatric disorders.