Pregnancy-associated breast cancer and pregnancy following treatment for breast cancer,in a cohort of women from Victoria,Australia, with a first diagnosis of invasive breast cancer

BackgroundThis study examined pregnancy-associated breast cancer (PABC) and pregnancy following treatment for breast cancer.MethodsWe analysed data from a questionnaire-based, prospective study of women diagnosed with breast cancer. Timing of diagnosis in relation to pregnancy was self-reported in the enrolment questionnaire. Women reported subsequent pregnancies in annual follow-up questionnaires, up to at least 5 years from diagnosis.ResultsWomen with PABC made up 3.3% of women <48 years at diagnosis and 14.3% of women aged <35 years at diagnosis. Nine of 46 (19.6%) women who were aged <40 years at diagnosis, and had either no children, or only one child, became pregnant subsequent to their diagnosis, and 8 experienced a live birth.DiscussionAs the number of women with PABC was small, conclusions from this study are limited. However, young women should be alert to PABC, especially in the post-partum period. Some women, with incomplete families at diagnosis, are choosing to have one or more pregnancies following treatment.     

Initial modelling and updates on cost effectiveness from the first 10 years of a spleen registry

Objective: To validate our estimates from our original model and re‐evaluate the cost‐effectiveness of Spleen Australia, the Australian post‐splenectomy registry, using our original model with updated model parameters based on advances in the literature and experience of the registry over the past decade. Methods: We revisited a decision model from 2005, comparing 1,000 hypothetical registered patients with asplenia or hyposplenism against 1,000 who were not registered, and updated the model parameters. The cost‐effectiveness of the registry was evaluated from a healthcare perspective in terms of additional cost per case of overwhelming post‐splenectomy infection (OPSI) avoided and as additional cost per life year gained. Results: Over a cohort lifetime the registry was associated with an additional cost of $125,724 per case of OPSI avoided or $19,286 per life year gained. Conclusions: Despite our initial over‐estimation of immunisation and chemoprophylaxis uptake and increases in unit costs, our re‐evaluation confirmed use of the registry to be cost‐effective. Implications for public health: Improved outcomes for patients with asplenia or hyposplenism can be achieved by a cost‐effective registry. Additional research into effectiveness of interventions, OPSI prevalence associated with varying intervention use, and compliance rates over time after registration would provide improved accuracy of cost‐effectiveness estimates.     

Imaging benign gynaecological conditions

Radiology continues to play an essential role in the management of benign gynaecological conditions. Multiple imaging modalities are utilised to investigate benign conditions: ultrasound; computed tomography and magnetic resonance imaging. Each modality has a different role in diagnosis, treatment selection and follow-up. This review discusses the different imaging modalities and their recommended roles in the imaging benign gynaecological conditions. The imaging findings of common benign female pelvic pathology are discussed and illustrated.     

High‐frequency p16INK4A promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16^INK4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation‐specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki‐67 index), p16^INK4A and SETDB1 expression were evaluated by immunohistochemistry. High‐frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16^INK4A promoter methylation was higher in vertical growth‐phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16^INK4A methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1–30%) p16^INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16^INK4A methylation and p16^INK4A expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0–5/mm² vs >5/mm², P = 0.0869), advanced Clark level (III‐V, P = 0.0380), epidermal involvement (P = 0.0331) and the non‐chronic sun exposure‐associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16^INK4A promoter and several prognostic parameters in melanomas.     

Healthcare provider knowledge,attitudes and practices in patients on the Victorian Spleen Registry

Objective: This study aimed to evaluate the knowledge, attitudes and practices of healthcare providers regarding asplenic patients and to assess their satisfaction with the Victorian Spleen Registry (VSR) service. Methods: Survey forms were sent to 992 healthcare providers listed as caring for at least one patient registered on the VSR. Results: A total of 223 completed questionnaires were returned. Healthcare providers heard about the VSR mainly from another healthcare professional or through a healthcare institution (31.7%), via online or printed resources (30.8%) or from their patients (24.4%). Most respondents valued the work of the VSR in providing information to healthcare professionals (71.4%), providing a reminder service for vaccinations (66.7%) and providing education to patients (60.5%). Most of those surveyed correctly identified high‐risk infections for asplenic and hyposplenic patients with encapsulated organisms, but less than one‐third identified a risk with malarial infections (32.9%). Providers always recommended influenza vaccinations, emergency standby antibiotics and an alert medallion or card in 92.8%, 63.6% and 36.4% of cases, respectively. Conclusions: Healthcare providers value and are satisfied with the service provided by the VSR. Patients can play a valuable role in communicating with their health providers. This survey may have been of value to healthcare providers by heightening awareness of the VSR website as well as knowledge of the registry. Implications: The results positively reflect the functioning of the VSR, although better promotion of the VSR among healthcare professionals and consideration of expansion is needed.     

Provider Response to Critical Action Values for Hypoglycemia in the Ambulatory Setting: a Retrospective Cohort Study

BackgroundThe blood glucose level triggering a critical action value (CAV) for hypoglycemia is not standardized, and associated outcomes are unknown.ObjectiveTo evaluate the clinical consequences of, and provider responses to, CAVs for hypoglycemia.DesignRetrospective cohort study at Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center between April 1, 2013, and January 31, 2017.ParticipantsPatients with an ambulatory serum glucose < 50 mg/dL. Point-of-care capillary glucose and whole blood glucose samples were excluded.Main MeasuresElectronic medical record (EMR) review for providers’ documented response to CAV, associated patient symptoms, and serious adverse events.Key ResultsWe analyzed 209 CAVs for hypoglycemia from 154 patients. The median age (IQR) was 59 years (46, 69), 89 (57.8%) were male, and 96 (62.3%) were black. Provider-to-patient contact occurred in 128 of 209 (61.2%) episodes, among which no documented etiology was observed for 81 of 128 (63.3%), no recommendations were provided in 32 of 128 (25.0%), and no patient-reported hypoglycemic symptoms were documented in 103 of 128 (80.5%). Serious adverse events were documented in 4 of 128 episodes (3.1%), two required glucagon administration, and three required an ED visit. Provider-to-patient contact was associated with the patient having malignant neoplasm (adjusted OR 3.63, p = 0.045) or a hypoglycemic disorder (adjusted OR 7.70, p = 0.018) and inversely associated with a longer time from specimen collection to EMR result (adjusted OR 0.90 per hour, p = 0.016).ConclusionsThere is inconsistent provider-to-patient contact following CAVs for hypoglycemia, and the etiology and symptoms of hypoglycemia were infrequently documented. There were few serious documented adverse events associated with hypoglycemia, although undocumented events may have occurred, and the incidence of serious adverse events in non-contacted patients remains unknown. These findings demonstrate a need to standardize provider response to CAVs for hypoglycemia. Decreasing the lag time between sample collection and laboratory result reporting may increase provider-to-patient contact.KEY WORDS: Hypoglycemia, Critical action value, Ambulatory, Glucose     

Density and function of inward currents in right atrial cells from chronically fibrillating canine atria

OBJECTIVE: To determine whether I(Na) and I(CaL) are altered in function/density in right atrial (RA) cells from dogs with chronic atrial fibrillation (cAF dogs, episodes lasting at least 6 days) and whether the changes that occur differ from those in dogs with nonsustained or brief episodes of fibrillation (nAF dogs). METHODS: Using whole cell voltage clamp, sodium and calcium current density and function were determined in disaggregated RA cells from nAF, cAF and control atria (Con). Ca(2+) currents were studied with either Ca(2+) or Ba(2+) as charge carrier, as well as with either EGTA or BAPTA as the internal solution Ca(2+) chelator. RESULTS: After rapid atrial pacing, dogs can either fibrillate for short periods of time (nAF) or longer, more sustained periods (cAF). Both the Na(+) and Ca(2+) current decrease in cells of the nAF atria. Na(+) current density remains reduced in cAF cells with some slowing of recovery kinetics. Ca(2+) current density does not further decrease with persistent atrial fibrillation (cAF cells) remaining significantly different from Con cells. However, the difference in density of Ca(2+) currents between nAF and Con cells is negligible when Ba(2+) is charge carrier and when Ca(i) is quickly and effectively chelated with BAPTA. On the contrary, cAF I(BaL) densities remain significantly reduced compared to Con and nAF values when Ba(2+)/BAPTA conditions are used. CONCLUSIONS: Na(+) current density/function does not recover to Con values in cAF. Further these enhanced Ca(2+)-dependent inactivation processes contribute significantly to the reduction of I(CaL) density observed in nAF cells while reduction of Ca(2+) currents in cAF atria is probably by another mechanism     

Epidemiology of sporadic bloody diarrhea in rural Western Kenya

We conducted laboratory-based surveillance and a case-control study to characterize the epidemiology of bloody diarrhea in rural Western Kenya. From May 1997 through April 2001, we collected stool from 451 persons with bloody diarrhea presenting to four rural clinics. Cultures of 231 (51%) specimens yielded 247 bacterial pathogens: 198 Shigella (97 S. flexneri, 41 S. dysenteriae type 1, 39 S. dysenteriae type non-1, 13 S. boydii, 8 S. sonnei), 33 Campylobacter, 15 non-typhoidal Salmonella, and 1 Vibrio cholerae O1. More than 90% of the isolates (excluding Campylobacter) were resistant to trimethoprim-sulfamethoxazole and tetracycline, and more than 80% were resistant to ampicillin. Most (74%) ill persons received medication to which their isolate was resistant. Drinking Lake Victoria water and sharing latrines between multiple households increased risk of bloody diarrhea. Washing hands after defecating was protective. Providing safe drinking water and more latrines, and promoting hand washing could reduce the burden of illness from bloody diarrhea while limiting injudicious antimicrobial use.     

New norms for a new generation: cognitive performance in the framingham offspring cohort

A previous publication presented normative data on neuropsychological tests stratified by age, gender, and education based on the Original Cohort of the Framingham Heart Study. Many contemporary investigations include subject samples with higher levels of education, a factor known to affect cognitive performance. Secular change in education prompted the reexamination of norms in the children of the Original Cohort. The study population consisted of 853 men and 988 women from the Offspring Study, free of clinical neurological disease, who underwent a neuropsychological examination, which included tests given to their parents in 1974 to 1976 as well as additional newer tests to provide a more comprehensive battery. The Offspring population overall was more evenly distributed by gender and better educated. Their performance on cognitive tests was superior to that of the Original Cohort. Multivariable analyses revealed that more years of education explained only a part of the cohort differences. These findings suggest that continued surveillance of each generation is necessary to document the impact that unique social and economic variables have on cognitive function. Here, the authors provide updated normative data.