Evaluation of breast involvement in relation to Cowden syndrome: a radiological and clinicopathological study of patients with PTEN germ-line mutations

We describe the clinical, radiological, and pathological findings of the diverse benign and malignant breast neoplasms found in association with Cowden syndrome. Patients with Cowden syndrome had a substantially increased risk of breast carcinoma. We find that 33% of the patients in our study population with Cowden disease have developed breast carcinoma to date. An association between Cowden disease and multiple tubular adenomas or breast hamartomas was found in two patients, suggesting a genetic origin. PTEN germ-line mutations were found in all four patients presenting with relevant benign or malignant breast pathology. We also assess the value of specific diagnostic tools used in the surveillance management. Screening mammography was useful in the diagnosis of small, high-grade carcinomas.     

Is it possible to refine the indication for sentinel node biopsy in high-risk ductal carcinoma in situ?

BACKGROUND: The indication for sentinel node biopsy (SNB) has not been fully established yet for patients with ductal carcinoma in situ (DCIS). AIM: To relate the conversion rate to invasive carcinoma with sentinel node positivity in high risk DCIS, and to refine the clinical presentation analysis in order to better select patients for SNB. For this purpose, a risk score was devised. METHODS: From 1998 to 2005, 151 high-risk DCIS patients from six clinical centres were included in a prospective sentinel node database. The conversion rate to invasive carcinoma was 39%. Ten of 142 (7%) successful SNBs showed a positive sentinel node (eight micrometastatic). The sentinel node was positive in 1% of pure DCIS, in 5.5% of DCIS with micro-invasion, and in 19.5% of invasive carcinoma. RESULTS: Both clinical presentation and corresponding risk score were closely related to conversion to invasive carcinoma. The association of risk score and sentinel node positivity approached but did not reach statistical significance (P=0.06); therefore a subset of further selected higher risk patients could not be defined. CONCLUSION: The relevance of SNB positivity cannot be overlooked in high-risk DCIS patients, however, because SNB is not free from morbidity and cost, more studies are needed to refine its final indication.     

Correlations of thalamic reductions with verbal fluency impairment in those born prematurely

Prematurity is associated with reduced brain volume, and the thalamus is among the structures most affected. We used a voxel-based morphometry analysis of gray matter to map regional atrophy in the thalamus in a sample of 30 adolescents with antecedents of very preterm birth. The preterm sample was compared with 30 controls matched by age, sex, handedness and sociocultural status. Individuals with very preterm birth differed from controls in several thalamic nuclei, and semantic and phonetic fluency showed different correlation patterns with brain volume. Semantic fluency achieved significant correlations with more thalamic nuclei than phonetic fluency. These results agree with functional magnetic resonance imaging studies showing that semantic fluency involves more cerebral regions than phonetic fluency.     

Impaired duration mismatch negativity in developmental dyslexia

A mismatch negativity event-related potential protocol was administered to dyslexic children and their respective controls to test whether a specific auditory deficit concerning phonetic processing or a lower level auditory processing deficit was present in developmental dyslexia. Three different contrast conditions were explored, including nonphonological sounds, contrasted in pitch and duration, and phonemes. Mismatch negativity amplitudes differed significantly between groups in the duration condition, whereas no differences were found in the frequency and phoneme conditions. Moreover, the dyslexic children had delayed mismatch negativity latencies in the three contrast conditions. Our results suggest a deficit in low-level auditory discrimination in dyslexic children, in particular when detecting stimulus duration, and support the rapid auditory processing theory of dyslexia.     

Concordance of the Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) with standardized clinical assessments in the WHO World Mental Health surveys

The DSM-IV diagnoses generated by the fully structured lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) in the WHO World Mental Health (WMH) surveys were compared to diagnoses based on follow-up interviews with the clinician-administered non-patient edition of the Structured Clinical Interview for DSM-IV (SCID) in probability subsamples of the WMH surveys in France, Italy, Spain, and the US. CIDI cases were oversampled. The clinical reappraisal samples were weighted to adjust for this oversampling. Separate samples were assessed for lifetime and 12-month prevalence. Moderate to good individual-level CIDI-SCID concordance was found for lifetime prevalence estimates of most disorders. The area under the ROC curve (AUC, a measure of classification accuracy that is not influenced by disorder prevalence) was 0.76 for the dichotomous classification of having any of the lifetime DSM-IV anxiety, mood and substance disorders assessed in the surveys and in the range 0.62-0.93 for individual disorders, with an inter-quartile range (IQR) of 0.71-0.86. Concordance increased when CIDI symptom-level data were added to predict SCID diagnoses in logistic regression equations. AUC for individual disorders in these equations was in the range 0.74-0.99, with an IQR of 0.87-0.96. CIDI lifetime prevalence estimates were generally conservative relative to SCID estimates. CIDI-SCID concordance for 12-month prevalence estimates could be studied powerfully only for two disorder classes, any anxiety disorder (AUC = 0.88) and any mood disorder (AUC = 0.83). As with lifetime prevalence, 12-month concordance improved when CIDI symptom-level data were added to predict SCID diagnoses. CIDI 12-month prevalence estimates were unbiased relative to SCID estimates. The validity of the CIDI is likely to be under-estimated in these comparisons due to the fact that the reliability of the SCID diagnoses, which is presumably less than perfect, sets a ceiling on maximum CIDI-SCID concordance.     

A multicentre randomized trial of combined individual and telephone counselling for smoking cessation

Objective

The present study assessed the effectiveness of smoking cessation programs combining individual and telephone counselling, compared to individual or telephone counselling alone.

Method

A randomized, multicentre, open-label trial was performed between January 2009 and July 2011 at six smoking cessation clinics in Spain. Of 772 smokers assessed for eligibility, 600 (77%) met inclusion criteria and were randomized. Smokers were randomized to receive individual counselling, combined telephone and individual counselling, or telephone counselling. The primary outcome was biochemically validated continuous abstinence at 52 weeks.

Results

The 52-week abstinence rate was significantly lower in the telephone group compared to the combined group (20.1% vs. 29.0%; OR, 1.32; 95% CI, 1.1–2.7) and to the individual counselling group (20.1% vs. 27.9%; OR, 1.37; 95% CI, 1.0–2.8). The 52-week abstinence rates were not significantly higher in the combined group than the individual group (OR, 0.97; 95% CI, 0.7–1.4).

Conclusion

Individual counselling and combined individual and telephone counselling were associated with higher 52-week abstinence rates than telephone counselling alone. A combined approach may be highly useful in the clinical treatment of smokers, as it involves less clinic visits than individual counselling alone, thus reducing the program cost, and it increases patient compliance compared to telephone counselling alone.     

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy

Introduction

HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired.

Methods

We analysed the response to vaccination (antiHAV titres ≥20 IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression.

Results

The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05–0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14–0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3–10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22–5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48–3.63).

Conclusion

The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers.     

Los estudiantes de medicina españoles y la medicina de familia. Datos de las 2 fases de una encuesta estatal

ObjectiveTo examine the perceptions and expectations about Family Practice (FP) and Primary Care (PC) in 1st, 3rd and 5th year students in medical schools.DesignAn observational study in two cross sections with intervals of two years.LocationSpanish Medical Schools.Participants1st, 3rd and 5th year students of 22 schools (1st phase) and 15 (second phase).Primary measurementsSelf-report questionnaires completed during the first quarter of the 2009-2010 and 2011-2012 academic years. It had 70 items in three blocks: perceptions of FP (19 items), training in FP (26 items), expectations and preferences (25 items), plus 13 specific items for 3rd and 5th year students. Most of the items were answered in a 6 point Likert scale.ResultsA total of 5299 responses in phase I, and 3869 in phase II were received. Students perceive FP and PC as essential areas of the health system and professional practice, but with little scientific and technical appeal. The large majortiy, 87%, consider training in FP necessary and compulsory, and it should start in third year. They prefer hospital medical specialities (88-89%), followed by surgical and paediatrics. FP is preferred by the 37-39%. Only between 24% and 28% of students have a clear preference for a specialty when they start medical studies.ConclusionsFP and PC are key areas and should be part of the curriculum, but are perceived to be of low scientific appeal.