Second cancers after medulloblastoma: population-based results from the United States and Sweden

Medulloblastoma, one of the most common central nervous system(CNS)tumors in children, requires aggressive multimodality therapy including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neo plasms in patients with histologically confirmed medulloblastoma (n = 1,262).Overall, there was a 5.4-fold excess of second neoplasms (95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight to 432 months after initial diagnosis(median, 73 months) with significantly elevated ratios for all intervals examined except for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands, cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15second cancers with treatment data, seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation exposure. This revised version was published online in July 2006 with corrections to the Cover Date.     

Sustainable maternity services in remote and rural Scotland? A qualitative survey of staff views on required skills, competencies and training

Objectives: To explore staff views on their roles, skills and training to deliver high quality and local intrapartum services in remote and rural settings against national recommendations.     

Cancer Incidence in Kentucky, Pennsylvania, and West Virginia: Disparities in Appalachia

CONTEXT: Composed of all or a portion of 13 states, Appalachia is a heterogeneous, economically disadvantaged region of the eastern United States. While mortality from cancer in Appalachia has previously been reported to be elevated, rates of cancer incidence in Appalachia remain unreported. PURPOSE: To estimate Appalachian cancer incidence by stage and site and to determine if incidence was greater than that in the United States. METHODS: Using 1994--1998 data from the central registries of Kentucky, Pennsylvania, and West Virginia, age-adjusted incidence rates were calculated for the rural and nonrural regions of Appalachia. These state rates were compared to rates from the Surveillance, Epidemiology, and End Results (SEER) program for the same years by calculating the adjusted rate ratio (RR) and a 95% confidence interval (CI). FINDINGS: Both the entire and rural Appalachian regions had an adjusted incidence rate for all cancer sites similar to the SEER rate (RR = 1.00 [95% CI, 1.00-1.01] and RR = 0.99 [95% CI, 0.99-1.00], respectively). However, incidence of cancer of the lung/ bronchus, colon, rectum, and cervix in Appalachia was significantly elevated (RR = 1.22 [95% CI, 1.20-1.23], 1.13 [95% CI, 1.11-1.14], 1.19 [95% CI, 1.16-1.22], and 1.12 [95% CI, 1.07-1.17], respectively). Incidence of cancer of the lung/bronchus and cervix in rural Appalachia was even more elevated (RR = 1.34 [95% CI, 1.31-1.36] and 1.29 [95% CI, 1.21-1.38], respectively). Incidence of unstaged disease for all cancer sites in Appalachia (RR = 1.06 [95% CI, 1.05-1.08]), particularly rural Appalachia (RR = 1.28 [95%CI, 1.25-1.301), was elevated. CONCLUSIONS: Cancer incidence in Appalachia was not found to be elevated. However, incidence of cancer of the lung/bronchus, colon, rectum, and cervix was elevated in Appalachia. The rates of unstaged cancer of every examined site were elevated in rural Appalachia, suggesting a lack of access to cancer health care.     

Airborne dispersal as a novel transmission route of coagulase-negative staphylococci: interaction between coagulase-negative staphylococci and rhinovirus infection.

OBJECTIVE: To investigate whether rhinovirus infection leads to increased airborne dispersal of coagulase-negative staphylococci (CoNS). DESIGN: Prospective nonrandomized intervention trial. SETTING: Wake Forest University School of Medicine, Winston-Salem, North Carolina. PARTICIPANTS: Twelve nasal Staphylococcus aureus-CoNS carriers among 685 students screened for S. aureus nasal carriage. INTERVENTIONS: Participants were studied for airborne dispersal of CoNS in a chamber under three conditions (street clothes, sterile gown with a mask, and sterile gown without a mask). After 2 days of pre-exposure measurements, volunteers were inoculated with a rhinovirus and observed for 14 days. Daily quantitative nasal and skin cultures for CoNS and nasal cultures for rhinovirus were performed. In addition, assessment of cold symptoms was performed daily, mucous samples were collected, and serum titers before and after rhinovirus inoculation were obtained. Sneezing, coughing, and talking events were recorded during chamber sessions. RESULTS: All participants had at least one nasal wash positive for rhinovirus and 10 developed a symptomatic cold. Postexposure, there was a twofold increase in airborne CoNS (P = .0004), peaking at day 12. CoNS dispersal was reduced by wearing a gown (57% reduction, P < .0001), but not a mask (P = .7). Nasal and skin CoNS colonization increased after rhinovirus infection (P < .05). CONCLUSIONS: We believe this is the first demonstration that a viral pathogen in the upper airways can increase airborne dispersal of CoNS in nasal S. aureus carriers. Gowns, gloves, and caps had a protective effect, whereas wearing a mask did not further reduce airborne spread.     

Solid lipid microparticles containing loratadine prepared using a Micromixer

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol® ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.     

Subnuclear partitioning of rRNA genes between the nucleolus and nucleoplasm reflects alternative epiallelic states

Eukaryotes can have thousands of 45S ribosomal RNA (rRNA) genes, many of which are silenced during development. Using fluorescence-activated sorting techniques, we show that active rRNA genes in Arabidopsis thaliana are present within sorted nucleoli, whereas silenced rRNA genes are excluded. DNA methyltransferase (met1), histone deacetylase (hda6), or chromatin assembly (caf1) mutants that disrupt silencing abrogate this nucleoplasmic–nucleolar partitioning. Bisulfite sequencing data indicate that active nucleolar rRNA genes are nearly completely demethylated at promoter CGs, whereas silenced genes are nearly fully methylated. Collectively, the data reveal that rRNA genes occupy distinct but changeable nuclear territories according to their epigenetic state.     

Pandemic Superimposed on Epidemic: Covid-19 Disparities in Black Americans

Health and healthcare disparities are variances in the health of a population or the care rendered to a population. Disparities result in a disproportionately higher prevalence of disease or lower standard of care provided to the index group. Multiple theories exist regarding the genesis of this disturbing finding. The COVID-19 pandemic has had the unfortunate effect of amplifying health inequity in vulnerable populations. African Americans, who make up approximately 12% of the US population are reportedly being diagnosed with COVID-19 and dying at disproportionately higher rates. Viewed holistically, multiple factors are contributing to the perfect storm: 1) Limited availability of public testing, 2) A dramatic increase in low wage worker unemployment/health insurance loss especially in the service sector of the economy, 3) High rates of preexisting chronic disease states/reduced access to early healthcare and 4) Individual provider and structural healthcare system bias. Indeed, COVID-19 represents a pandemic superimposed on a historic epidemic of racial health inequity and healthcare disparities. Therapeutic solutions are not expected in the near term. Thus, identifying the genesis and magnitude of COVID-19's impact on African American communities is the requisite first step toward crafting an immediate well designed response. The mid and long term approach should incorporate population health based tactics and strategies.