NOD2/CARD15 gene variants are linked to failure of antibiotic treatment in perianal fistulating Crohn's disease

OBJECTIVES:  The Crohn's disease (CD) susceptibility gene, nucleotide-binding oligomerizetion domain 2 (NOD2)/caspase recruitment domain 15 (CARD15), is linked to the innate immune response associated with altered epithelial bacterial defense. Its relevance in antibiotic therapy of perianal fistulating CD remains elusive. The aim of the study was to explore systematically the association between NOD2/CARD15 variants and clinical response of perianal fistulas in patients using antibiotic therapy.
METHODS:  Fifty-two patients (median age 36 yr) with draining perianal fistulas were treated with ciprofloxacin (N = 49) or metronidazole (N = 3) for a median duration of 7 wk. Complete response was defined as the absence of any draining fistula despite gentle finger compression. Genotyping for NOD2/CARD15 variants and human beta (β)-defensin 2 (HBD-2) copies was performed by 5' nuclease assays (Applied Biosystems, Foster City, CA). The examiners and laboratory investigators were blinded. The Fisher exact test and Wilcoxon signed rank test were used for statistical analysis.
RESULTS:  Ciprofloxacin was discontinued in one patient due to diarrhea after 2 wk. Complete fistula response was observed in 13 of 39 patients with NOD2/CARD15 wild-type (33.3%) compared with none in patients carrying NOD2/CARD15 variants (0%, P = 0.02). The median number of HBD-2 gene copies between responders and partial/nonresponders was similar.
CONCLUSIONS:  The study result suggests a substantial contribution of NOD2/CARD15 to the antibiotic treatment outcome of perianal fistulating CD. NOD2/CARD15 variants may predispose to an altered intestinal microflora in perianal fistulas that is less responsive to antibiotic treatment.     

Capsaicin 8% Patch in Painful Diabetic Peripheral Neuropathy: A Randomized,Double-Blind,Placebo-Controlled Study

This 12-week study evaluated the efficacy and safety of capsaicin 8% patch versus placebo patch in painful diabetic peripheral neuropathy (PDPN). Patients aged 18 years or older with PDPN were randomized (1:1) to one 30-minute treatment (capsaicin 8% patch or placebo patch) to painful areas of the feet. Overall, 369 patients were randomized (capsaicin 8% patch, n = 186; placebo patch, n = 183). Percentage reduction in average daily pain score from baseline to between weeks 2 through 8 (the primary end point) was statistically significant for capsaicin 8% patch versus placebo (?27.4% vs ?20.9%; P = .025); improvements in pain were observed from week 2 onward. Versus placebo, patients treated with capsaicin 8% patch had a shorter median time to treatment response (19 vs 72 days) and modest improvements in sleep interference scores from baseline to between weeks 2 through 8 (P = .030) and weeks 2 through 12 (P = .020). Apart from application site reactions, treatment-emergent adverse events were similar between groups. No indications of deterioration in sensory perception of sharp, cold, warm, or vibration stimuli were observed. In patients with PDPN, capsaicin 8% patch treatment provided modest pain relief and sleep quality improvements versus a placebo patch, similar in magnitude to other treatments with known efficacy, but without systemic side effects or sensory deterioration.

Pathogenesis and pathophysiology of pneumococcal meningitis

Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.     

Worsening of psychosis in schizophrenia is longitudinally associated with tardive dyskinesia in the European Schizophrenia Outpatient Health Outcomes study

OBJECTIVE: The objective of the study was to examine if worsening of psychosis predicts the emergence of tardive dyskinesia (TD). METHOD: Global measures of TD and Clinical Global Impression (CGI) overall symptom severity score were rated in 4 assessments in 12 months. In a risk set free of TD at baseline, associations between TD onset and change in CGI scores were assessed using Cox proportional hazard regression. RESULTS: A total of 8,620 patients yielded 23,565 follow-up observations, 8.8% of which represented a worsening in CGI overall symptom severity relative to the previous observation, yielding an incidence of TD of 5.2%, compared with 2.7% in observations without worsening of psychopathology (rate ratio, 1.9; 95% confidence interval, 1.3-2.7). Incidence of TD was longitudinally associated with a worsening of the CGI overall symptom severity in the months preceding TD onset (adjusted hazard ratio over 6 levels of CGI score, 1.3; 95% confidence interval, 1.1-1.4). CONCLUSION: Worsening in overall psychopathology in schizophrenia is longitudinally associated with the emergence of TD as measured by CGI overall symptom severity.     

Cognitive outcome in adults after bacterial meningitis

Objective

To evaluate cognitive outcome in adult survivors of bacterial meningitis.

Methods

Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls.

Results

Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self‐reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar.

Conclusions

Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.The estimated annual incidence of bacterial meningitis is 4–6 per 100 000 adults and Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the causative bacteria in 80% of cases.^1,2 Fatality rates in patients with pneumococcal meningitis (26%) and meningococcal meningitis (7%) are significant.^1,2,3 Even in patients with apparent good recovery, cognitive impairment occurs frequently,⁴ especially after pneumococcal meningitis.^4,5,6 The cognitive functions affected by bacterial meningitis differ between studies, most likely because of the limited numbers of patients examined, and the lack of uniformity across studies in assessment methods and in the definition of cognitive impairment.^{4,5,6,7,8,9,10} We therefore pooled data on cognitive outcome after bacterial meningitis from three of our previous studies to more clearly determine which cognitive functions are affected by bacterial meningitis and to identify which patients are at risk of developing cognitive impairment.     

Coping strategies as determinants of quality of life in stroke patients: a longitudinal study

BACKGROUND: Quality of life (QoL) is reduced for stroke patients and coping strategies have been suggested as determinants of QoL. Thus far the relationship between coping and QoL has only been examined in small-scale cross-sectional designs. Therefore, the current study set out to examine this relationship in a longitudinal setting. METHODS: Stroke patients who were discharged home were interviewed at 4 different time points; just before discharge (T1), and 2 months (T2), 5 months (T3) and 9-12 months after discharge (T4). QoL was measured by the EQ-5D index score and the SF-36 utility score and coping expressed in terms of tenacious goal pursuit and flexible goal adjustment. Modified Rankin scale was assessed as a measure of general functioning. RESULTS: Eighty stroke patients were included. Coping was not predictive of QoL at T1 and T2 but rather at T3 and T4. At T4 both coping strategies determined the levels of QoL as measured with the EQ-5D index score; higher levels of tenacious goal pursuit as well as flexible goal adjustment were associated with higher levels of QoL. This regression model explained 44% of the variance. CONCLUSIONS: Coping is a powerful determinant of QoL, but only more than 5 months after discharge; before this time QoL is mainly determined by general functioning. Both coping strategies were important determinants of QoL.