Association between administration of hepatitis B vaccine at birth and completion of the hepatitis B and 4:3:1:3 vaccine series

CONTEXT: The association between infant age at initiation of hepatitis B vaccination and completion of the 3-dose hepatitis B vaccination series is unclear. OBJECTIVE: To assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles-containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine). DESIGN, SETTING, AND PARTICIPANTS: Analysis of data from the 1998 National Immunization Survey, a random-digit-dialing telephone survey (n = 34,480 completed interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey. MAIN OUTCOME MEASURES: Percentage of infants who received at least 3 doses of hepatitis B vaccine and percentage who received the 4:3:1:3 vaccine series, by age at receipt of the first dose of hepatitis B vaccine. RESULTS: Overall, 86.9% of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9% completed the 4:3:1:3 vaccine series. Multivariate analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios (ORs) for not completing the 3-dose hepatitis B vaccine series among children who received the first dose at 8 to 41 days, 42 to 91 days, 92 to 182 days, 183 to 273 days, and 274 or more days of age were 2.4 (95% confidence interval [CI], 2.0-3.0), 7.8 (95% CI, 6.5-9.3), 9.6 (95% CI, 7.0-13. 3), 18.3 (95% CI, 12.0-28.0), and 46.6 (95% CI, 33.7-64.5), respectively; ORs for not completing the 4:3:1:3 vaccine series among these same groups were 1.0 (95% CI, 0.8-1.1), 1.0 (95% CI, 0. 8-1.1), 1.7 (95% CI, 1.3-2.3), 3.8 (95% CI, 2.6-5.6), and 4.0 (95% CI, 2.9-5.5), respectively. CONCLUSION: Administration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series. JAMA. 2000;284:978-983     

Trypanosoma cruzi genotypes of insect vectors and patients with Chagas of Chile studied by means of Cytochrome b gene sequencing, minicircle hybridization, and nuclear gene polymorphisms

Fifty-six Trypanosoma cruzi stocks from Chile and neighboring countries and different hosts, humans, and Triatoma infestans and Mepraia sp., vectors of domiciliary and natural environments were characterized by using three molecular markers. These were cytochrome b (Cyt b) gene sequencing, minicircle DNA blotting, and hybridization with five genotype-specific DNA probes and nuclear analysis of 1f8 and gp72 by polymerase chain reaction-restriction fragment length polymorphism. The results with all three molecular markers are concordant, with minor limitations, grouping T. cruzi stocks into four discrete typing units (DTUs) (TcI, TcII, TcV, and TcVI). TcI and TcII stocks were heterogeneous. TcI and TcII stocks were clustered in two main subgroups determined by Cyt b gene sequencing and minicircle hybridization. However, TcV and TcVI stocks were homogeneous and not differentiated by Cyt b gene sequencing or minicircle DNA hybridization. The discriminatory power and limitations of the molecular markers are discussed, as well as the distribution of the four DTUs in the domiciliary and sylvatic transmission cycles of Chile and the limitations of each marker for molecular epidemiological studies performed with T. cruzi stocks rather than the analysis of direct T. cruzi samples from natural hosts.     

Interaction between the dihydropyridine receptor Ca2+ channel beta-subunit and ryanodine receptor type 1 strengthens excitation-contraction coupling

Previous studies have shown that the skeletal dihydropyridine receptor (DHPR) pore subunit Ca(V)1.1 (alpha1S) physically interacts with ryanodine receptor type 1 (RyR1), and a molecular signal is transmitted from alpha1S to RyR1 to trigger excitation-contraction (EC) coupling. We show that the beta-subunit of the skeletal DHPR also binds RyR1 and participates in this signaling process. A novel binding site for the DHPR beta1a-subunit was mapped to the M(3201) to W(3661) region of RyR1. In vitro binding experiments showed that the strength of the interaction is controlled by K(3495)KKRR_ _R(3502), a cluster of positively charged residues. Phenotypic expression of skeletal-type EC coupling by RyR1 with mutations in the K(3495)KKRR_ _R(3502) cluster was evaluated in dyspedic myotubes. The results indicated that charge neutralization or deletion severely depressed the magnitude of RyR1-mediated Ca(2+) transients coupled to voltage-dependent activation of the DHPR. Meantime the Ca(2+) content of the sarcoplasmic reticulum was not affected, and the amplitude and activation kinetics of the DHPR Ca(2+) currents were slightly affected. The data show that the DHPR beta-subunit, like alpha1S, interacts directly with RyR1 and is critical for the generation of high-speed Ca(2+) signals coupled to membrane depolarization. These findings indicate that EC coupling in skeletal muscle involves the interplay of at least two subunits of the DHPR, namely alpha1S and beta1a, interacting with possibly different domains of RyR1.     

Absence of the β subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the α1 subunit and eliminates excitation-contraction coupling

The multisubunit (α_1S, α₂/δ, β₁, and γ) skeletal muscle dihydropyridine receptor transduces transverse tubule membrane depolarization into release of Ca²⁺ from the sarcoplasmic reticulum, and also acts as an L-type Ca²⁺ channel. The α_1S subunit contains the voltage sensor and channel pore, the kinetics of which are modified by the other subunits. To determine the role of the β₁ subunit in channel activity and excitation-contraction coupling we have used gene targeting to inactivate the β₁ gene. β₁-null mice die at birth from asphyxia. Electrical stimulation of β₁-null muscle fails to induce twitches, however, contractures are induced by caffeine. In isolated β₁-null myotubes, action potentials are normal, but fail to elicit a Ca²⁺ transient. L-type Ca²⁺ current is decreased 10- to 20-fold in the β₁-null cells compared with littermate controls. Immunohistochemistry of cultured myotubes shows that not only is the β₁ subunit absent, but the amount of α_1S in the membrane also is undetectable. In contrast, the β₁ subunit is localized appropriately in dysgenic, mdg/mdg, (α_1S-null) cells. Therefore, the β₁ subunit may not only play an important role in the transport/insertion of the α_1S subunit into the membrane, but may be vital for the targeting of the muscle dihydropyridine receptor complex to the transverse tubule/sarcoplasmic reticulum junction.     

Navigating the Murky Waters of Colorectal Cancer Screening and Health Reform

The Affordable Care Act (ACA) mandates that both Medicaid and insurance plans cover life-saving preventive services recommended by the US Preventive Services Task Force, including colorectal cancer (CRC) screening and choice between colonoscopy, flexible sigmoidoscopy, and fecal occult blood testing (FOBT).People who choose FOBT or sigmoidoscopy as their initial test could face high, unexpected, out-of-pocket costs because the mandate does not cover needed follow-up colonoscopies after positive tests. Some people will have no coverage for any CRC screening because of lack of state participation in the ACA or because they do not qualify (e.g., immigrant workers).Existing disparities in CRC screening and mortality will worsen if policies are not corrected to fully cover both initial and follow-up testing.Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States,1 but many of these deaths could be averted by screening, which decreases both CRC incidence and mortality by 30% to 60%.2 The US Preventive Services Task Force strongly recommends CRC screening for adults aged 50 to 75 years by 3 evidence-based methods: annual fecal occult blood testing (FOBT) with either high-sensitivity guaiac or fecal immunochemical tests, flexible sigmoidoscopy every 5 years with interval FOBT, or colonoscopy every 10 years.3 In large randomized trials, FOBT and sigmoidoscopy reduced CRC incidence and mortality in 2-part screening programs in which initial positive FOBT or sigmoidoscopy was followed by a colonoscopy. Colonoscopy as an initial screening test is supported by observational studies.2 CRC screening by any of the recommended options is cost-effective,4,5 and potentially cost saving, because it reduces the number of patients needing advanced CRC treatment.6 However, to reduce CRC morbidity, mortality, and associated costs, screening must be increased beyond its current rates.     

Brain metastasis and carcinomatous meningitis from vulvar squamous cell carcinoma: case report

BACKGROUND: Brain metastasis and carcinomatous meningitis from gynecological tumors are an uncommon event, usually related to choriocarcinoma, ovarian and cervical cancer. CASE: A 74-year-old woman was diagnosed with locally advanced vulvar squamous carcinoma. Initial therapy consisted of multiagent chemotherapy and vulvar, pelvis and groin irradiation. The patient subsequently developed widely spread metastatic disease including brain and meningeal metastases. CONCLUSION: The rising incidence of central nervous system metastasis in the last two decades is probably associated with treatment-related improvement in life expectancy. To our knowledge, this is the first case reported of brain metastases and meningeal carcinomatosis associated with vulvar squamous cell carcinoma.     

Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention–sponsored Summit

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.