Occult axillary lymph node metastases are of no prognostic significance in breast cancer

The significance of occult metastases in axillary lymph nodes in patients with carcinoma of the breast is controversial. Additional sections were cut from the axillary lymph nodes of 477 women with invasive carcinoma of the breast, in whom no metastases were seen on initial assessment of haematoxylin and eosin stained sections of the nodes. One section was stained with haematoxylin and eosin, and one using immunohistochemistry with two anti-epithelial antibodies (CAM5.2 and HMFG2). Occult metastases were found in 60 patients (13%). The median follow-up was 18.9 years with 153 breast cancer related deaths. There was no difference in survival between those with and those without occult metastases. Multivariate analysis, however, showed that survival was related to tumour size and histological grade. This node-negative group was compared with a second group of 202 patients who had one involved axillary node found on initial assessment of the haematoxylin and eosin sections; survival was worse in the patients in whom a nodal metastasis was found at the time of surgery. Survival was not related to the size of nodal metastases in the occult metastases and single node positive groups. Some previous studies have found a worse prognosis associated with occult metastases on univariate analysis, but the evidence that it is an independent prognostic factor on multivariate analysis is weak. We believe that the current evidence does not support the routine use of serial sections or immunohistochemistry for the detection of occult metastases in the management of lymph node negative patients, but that the traditional factors of histological grade and tumour size are useful

Individual, community, and social network influences on beliefs concerning the acceptability of intimate partner violence in rural Senegal

Intimate partner violence (IPV) is a pressing international public health and human rights concern. Recent scholarship concerning causes of IPV has focused on the potentially critical influence of social learning and influence in interpersonal interaction through social norms. Using sociocentric network data from all individuals aged 16 years and above in a rural Senegalese village surveyed as part of the Niakhar Social Networks and Health Project (n =1,274), we estimate a series of nested linear probability models to test the association between characteristics of respondents' social networks and residential compounds (including educational attainment, health ideation, socioeconomic status, and religion) and whether respondents are classified as finding IPV acceptable, controlling for individual characteristics. We also test for direct social learning effects, estimating the association between IPV acceptability among network members and co-residents and respondents' own, net of these factors. We find individual, social network, and residential compound factors are all associated with IPV acceptability. On the individual level, these include gender, traditional health ideation, and household agricultural investment. Residential compound-level associations are largely explained in the presence of the individual and network characteristics, except for that concerning educational attainment. We find that network alters' IPV acceptability is strongly positively associated with respondents'own, net of individual and compound-level characteristics. A 10% point higher probability of IPV acceptability in respondents' networks is estimated in to be associated with a 4.5% point higher likelihood of respondents being classified as finding IPV acceptable. This research provides compelling evidence that social interaction through networks exerts an important, potentially normative, influence on whether individuals in this population perceive IPV as acceptable or not. It also suggests that interventions targeting individuals most likely to perceive IPV as acceptable may have a multiplier effect, influencing the normative context of others they interact with through their social networks

Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a service setting.

BACKGROUND: Muir-Torre syndrome (MTS) is a subtype of Lynch syndrome, which encompasses the combination of sebaceous skin tumours or keratoacanthomas and internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous neoplasms (SNs) may occur before other malignancies, and may lead to the diagnosis, which allows testing of other family members, cancer surveillance, risk-reducing surgery or prevention therapies. AIM: To evaluate the efficacy of universal immunohistochemistry (IHC) screening of SNs in a service setting. METHODS: Patients with SNs were ascertained by a regional clinical pathology service over a 3-year period. Results of tumour IHC, clinical genetics notes and germline genetic testing were retrospectively reviewed. RESULTS: In total, 62 patients presented with 71 SNs; 9 (15%) of these patients had previously diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients (94%); 26 (52%) had loss of staining of one or more mismatch repair proteins. Fifteen patients were referred to the Clinical Genetics department, and 10 patients underwent germline genetic testing. Two had a new diagnosis of MTS confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2 genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old woman with a sebaceous adenoma and history of endometrial cancer; to our knowledge, this is the first time a PMS2 mutation has been reported in MTS. CONCLUSIONS: Universal IHC screening of SNs is an effective method to identify cases for further genetic evaluation. Rates of referral to clinical genetics were only moderate (58%). Increased awareness of MTS could help improve the rate of onward referral

Social learning, influence, and ethnomedicine : individual, neighborhood and social network influences on attachment to an ethnomedical cultural model in rural Senegal

The preference in many parts of the world for ethnomedical therapy over biomedical alternatives has long confounded scholars of medicine and public health. In the anthropological literature cultural and interactional contexts have been identified as fundamental mechanisms shaping adherence to ethnomedical beliefs and health seeking behaviors. In this paper, we examine the association between individual, neighborhood, and social network characteristics and the likelihood of attachment to an ethnomedical cultural model encompassing beliefs about etiology of disease, appropriate therapeutic and preventative measures, and more general beliefs about metaphysics and the efficacy of health systems in a rural population in Eastern Senegal. Using data from a unique social network survey, and supplemented by extensive qualitative research, we model attachment to the ethnomedical model at each of these levels as a function of demographic, economic and ideational characteristics, as well as perceived effectiveness of both biomedical and ethnomedical therapy. Individuals' attachment to the ethnomedical cultural model is found to be strongly associated with characteristics of their neighborhoods, and network alters. Experiences with ethnomedical care among neighbors, and both ethnomedical and biomedical care among network alters, are independently associated with attachment to the ethnomedical model, suggesting an important mechanism for cultural change. At the same time, we identify an independent association between network alters' cultural models and those of respondents, indicative of a direct cultural learning or influence mechanism, modified by the degree of global transitivity, or 'connectedness' of individuals' networks. This evidence supports the long held theoretical position that symbolic systems concerning illness and disease are shared, reproduced, and changed through mechanisms associated with social interaction. This has potentially important implications not only for public health programming, but for the understanding of the reproduction and evolution of cultural systems more generally

The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes

Background. Type 1 diabetes (T1D) results from loss of immune regulation, leading to the development of autoimmunity to pancreatic β cells, involving autoreactive T effector cells (Teffs). Tregs, which prevent autoimmunity, require IL-2 for maintenance of immunosuppressive functions. Using a response-adaptive design, we aimed to determine the optimal regimen of aldesleukin (recombinant human IL-2) to physiologically enhance Tregs while limiting expansion of Teffs. Methods. DILfrequency is a nonrandomized, open-label, response-adaptive study of participants, aged 18–70 years, with T1D. The initial learning phase allocated 12 participants to 6 different predefined regimens. Then, 3 cohorts of 8 participants were sequentially allocated dose frequencies, based on repeated interim analyses of all accumulated trial data. The coprimary endpoints were percentage change in Tregs and Teffs and CD25 (α subunit of the IL-2 receptor) expression by Tregs, from baseline to steady state. Results. Thirty-eight participants were enrolled, with thirty-six completing treatment. The optimal regimen to maintain a steady-state increase in Tregs of 30% and CD25 expression of 25% without Teff expansion is 0.26 × 106 IU/m2 (95% CI –0.007 to 0.485) every 3 days. Tregs and CD25 were dose-frequency responsive, Teffs were not. The commonest adverse event was injection site reaction (464 of 694 events). Conclusions. Using a response-adaptive design, aldesleukin treatment can be optimized. Our methodology can generally be employed to immediately access proof of mechanism, thereby leading to more efficient and safe drug development